American Society for Reproductive Medicine (ASRM). Professional society whose affiliate organization, the Society for Assisted Reproductive Technology (SART), is composed of clinics and programs that provide ART.

ART (assisted reproductive technology). All treatments or procedures that include the handling of human eggs or embryos to help a woman become pregnant. ART includes but is not limited to in vitro fertilization (IVF), gamete intrafallopian transfer (GIFT), zygote intrafallopian transfer (ZIFT), tubal embryo transfer, egg and embryo cryopreservation, egg and embryo donation, and gestational surrogacy.

ART cycle. An ART cycle starts when a woman begins taking fertility drugs or having her ovaries monitored for follicle production. If eggs are produced, the cycle progresses to egg retrieval. Retrieved eggs are combined with sperm to create embryos. If fertilization is successful, at least one embryo is selected for transfer. If implantation occurs, the cycle may progress to clinical pregnancy and possibly live-birth delivery. ART cycles include any process in which (1) an ART procedure is performed, (2) a woman has undergone ovarian stimulation or monitoring with the intent of having an ART procedure, or (3) frozen embryos have been thawed with the intent of transferring them to a woman.

Canceled cycle. An ART cycle in which ovarian stimulation was performed but the cycle was stopped before eggs were retrieved or before embryos were transferred. Cycles are canceled for many reasons: eggs may not develop, the patient may become ill, or the patient may choose to stop treatment.

Cryopreservation. The practice of freezing eggs or embryos from a patient’s ART cycle for potential future use.

Diminished ovarian reserve. This diagnosis means that the ability of the ovary to produce eggs is reduced. Reasons include congenital, medical, or surgical causes.

Donor egg cycle. An ART cycle in which an embryo is formed from the egg of one woman (the donor) and then transferred to another woman (the recipient). Sperm from either the recipient’s partner or a donor may be used.

Donor embryo cycle. An ART cycle in which an embryo that is donated by a patient or couple who previously underwent ART treatment and had extra embryos available is transferred to another woman (the recipient).

Ectopic pregnancy. A pregnancy in which the fertilized egg implants in a location outside of the uterus—usually in the fallopian tube, the ovary, or the abdominal cavity. Ectopic pregnancy is a dangerous condition that must receive prompt medical treatment.

Egg. A female reproductive cell, also called an oocyte or ovum.

Egg/Embryo banking cycle. An ART cycle started with the intention of freezing (cryopreserving) all resulting eggs or embryos for potential future use.

Egg retrieval (also called oocyte retrieval). A procedure to collect the eggs contained in the ovarian follicles.

Egg transfer (also called oocyte transfer). The transfer of retrieved eggs into a woman’s fallopian tubes through laparoscopy. This procedure is used only in GIFT.

Embryo. An egg that has been fertilized by a sperm and has then undergone one or more cell divisions.

Embryo transfer. Placement of embryos into a woman’s uterus through the cervix after IVF. In zygote intrafallopian transfer, zygotes are placed in a woman’s fallopian tube.

Endometriosis. A medical condition that involves the presence of tissue similar to the uterine lining in locations outside the uterus such as the ovaries, fallopian tubes, or abdominal cavity.

Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA). Law passed by the United States Congress in 1992 requiring all clinics performing ART in the United States to annually report their success rate data to the Centers for Disease Control and Prevention.

Fertility preservation cycle. An ART cycle started with the intent of freezing and banking all eggs or embryos for at least 12 months for future use.

Fertilization. The penetration of the egg by the sperm and the resulting combining of genetic material that develops into an embryo.

Fetus. The unborn offspring from the eighth week after conception to the moment of birth.

Follicle. A structure in the ovaries that contains a developing egg.

Fresh eggs, sperm, or embryos. Eggs, sperm, or embryos that have not been frozen.

Fresh embryo cycle. An ART cycle in which fresh (never frozen) embryos are transferred to the woman. The fresh embryos are conceived with fresh or frozen eggs and fresh or frozen sperm.

Frozen egg cycle. An ART cycle in which frozen (cryopreserved) eggs are thawed, fertilized, and then the resulting fresh embryo is transferred to the woman. Frozen and thawed eggs may be fertilized with either fresh or frozen sperm.

Frozen embryo cycle. An ART cycle in which frozen (cryopreserved) embryos are thawed and transferred to the woman. Frozen embryos may have been conceived using fresh or frozen eggs and fresh or frozen sperm.

Gamete. A reproductive cell, either a sperm or an egg.

Gestational age. The deviation of time from estimated last menstrual period (LMP) to birth. LMP is estimated using the date of retrieval or transfer.

Gestational carrier (also called a gestational surrogate). A woman who gestates, or carries, an embryo that was formed from the egg of another woman with the expectation of returning the infant to its intended parents.

Gestational sac. A fluid-filled structure that develops within the uterus early in pregnancy. In a normal pregnancy, a gestational sac contains a developing fetus.

GIFT (gamete intrafallopian transfer). An ART procedure that involves removing eggs from the woman’s ovary and using a laparoscope to place the unfertilized eggs and sperm into the woman’s fallopian tube through small incisions in her abdomen.

ICSI (intracytoplasmic sperm injection). A procedure in which a single sperm is injected directly into an egg; this procedure is commonly used to overcome male infertility problems.

Implantation rate. A measurement of ART success when the ART cycle results in an intrauterine

clinical pregnancy, defined as the larger of either the number of maximum fetal hearts by ultrasound or maximum infants born, including live-birth deliveries and stillbirths, out of the total number of embryos transferred.

Infertility. In general, infertility refers to the inability to conceive after 12 months of unprotected intercourse. Women aged 35 and older unable to conceive after 6 months of unprotected intercourse generally are considered infertile for the purpose of initiating medical treatment.

IUI (intrauterine insemination). A medical procedure that involves placing sperm into a woman’s uterus to facilitate fertilization. IUI is not considered an ART procedure because it does not involve the manipulation of eggs.

IVF (in vitro fertilization). An ART procedure that involves removing eggs from a woman’s ovaries and fertilizing them outside her body. The resulting embryos are then transferred into a woman’s uterus through the cervix.

Live-birth delivery. The delivery of one or more infants with at least one alive.

Male factor infertility. Any cause of infertility due to low sperm count or problems with sperm function that makes it difficult for a sperm to fertilize an egg under normal conditions.

Miscarriage (also called spontaneous abortion). A pregnancy ending in the spontaneous loss of the embryo or fetus before 20 weeks of gestation.

Multiple-fetus pregnancy. A pregnancy with two or more fetuses, determined by the number of fetal hearts observed on an ultrasound.

Multiple live-birth delivery. The delivery of more than one infant with at least one born live.

NASS (National ART Surveillance System). Web-based data collection system used by all ART clinics to report data for each ART procedure to CDC.

Oocyte. The female reproductive cell, also called an egg.

Other reason, infertility. Reason for using ART including immunological problems, chromosomal abnormalities, cancer chemotherapy, and serious illnesses.

Other reason, non-infertility. Reason for using ART not related to infertility and not unexplained or unknown.

Ovarian hyperstimulation syndrome. A possible complication of ovarian stimulation or ovulation induction that can cause enlarged ovaries, a distended abdomen, nausea, vomiting or diarrhea, fluid in the abdominal cavity or chest, breathing difficulties, changes in blood volume or viscosity, and diminished kidney perfusion and function.

Ovarian monitoring. The use of ultrasound, or blood or urine tests to monitor follicle development and hormone production.

Ovarian stimulation. The use of drugs (oral or injected) to stimulate the ovaries to develop follicles and eggs.

Ovulatory dysfunction. A diagnostic category used when a woman’s ovaries are not producing eggs normally. It is usually characterized by irregular menstrual cycles reflective of ovaries that are not producing one mature egg each month. It includes polycystic ovary syndrome and multiple ovarian cysts.

Patient (nondonor) cycle. An ART cycle in which an embryo is formed from the egg of the patient and either partner or donor sperm and then transferred back to the patient.

PGT (preimplantation genetic testing). Diagnostic or screening techniques performed on embryos prior to transfer for detecting specific genetic conditions to reduce the risk of passing inherited diseases to children or screening for an abnormal number of chromosomes, which is of special value for patients with advanced age, recurrent miscarriages, or prior failed IVF.

Pregnancy (clinical). A pregnancy documented by ultrasound that shows a gestational sac in the uterus. For ART data reporting purposes, pregnancy is defined as a clinical pregnancy rather than a chemical pregnancy (positive pregnancy test).

SET (single embryo transfer). Single embryo transfer is a procedure in which one embryo, regardless of how many embryos are available, is placed in the uterus or fallopian tube. The embryo selected for SET might be a frozen (cryopreserved) embryo from a previous IVF cycle or a fresh embryo yielded during the current fresh IVF cycle.

Singleton live-birth delivery. The delivery of a single infant born alive.

Society for Assisted Reproductive Technology (SART). An affiliate of ASRM composed of clinics and programs that provide ART.

Sperm. The male reproductive cell.

Spontaneous abortion. See Miscarriage.

Stillbirth. The birth of an infant that shows no sign of life after 20 or more weeks of gestation.

Stimulated cycle. An ART cycle in which a woman receives oral or injected fertility drugs to stimulate her ovaries to develop follicles that contain mature eggs.

Thawed embryo cycle. Same as frozen embryo cycle.

Tubal factor infertility. A diagnostic category used when the woman’s fallopian tubes are blocked

or damaged, making it difficult for the egg to be fertilized or for an embryo to travel to the uterus.

Ultrasound. A technique used in ART for visualizing the follicles in the ovaries, the gestational sac, or the fetus.

Unexplained infertility. A diagnostic category used when no cause of infertility is found in either the woman or the man.

Unstimulated cycle. An ART cycle in which the woman does not receive drugs to stimulate her ovaries to produce more follicles and eggs. Instead, follicles and eggs develop naturally.

Uterine factor infertility. A structural or functional disorder of the uterus that results in reduced fertility.

ZIFT (zygote intrafallopian transfer). An ART procedure in which eggs are collected from a woman’s ovary and fertilized outside her body. A laparoscope is then used to place the resulting zygote into the woman’s fallopian tube through a small incision in her abdomen.

Zygote. A fertilized egg before it begins to divide.

During cleavage, the cells divide without an increase in mass; that is, one large single-celled zygote divides into multiple smaller cells. Each cell within the blastula is called a blastomere.

The maternal portion of the placenta develops from the deepest layer of the endometrium, the decidua basalis. To form the embryonic portion of the placenta, the syncytiotrophoblast and the underlying cells of the trophoblast (cytotrophoblast cells) begin to proliferate along with a layer of extraembryonic mesoderm cells. These form the chorionic membrane, which envelops the entire conceptus as the chorion. The chorionic membrane forms finger-like structures called chorionic villi that burrow into the endometrium like tree roots, making up the fetal portion of the placenta. The cytotrophoblast cells perforate the chorionic villi, burrow farther into the endometrium, and remodel maternal blood vessels to augment maternal blood flow surrounding the villi. Meanwhile, fetal mesenchymal cells derived from the mesoderm fill the villi and differentiate into blood vessels, including the three umbilical blood vessels that connect the embryo to the developing placenta.

The placenta develops throughout the embryonic period and during the first several weeks of the fetal period; placentation is complete by weeks 14–16. As a fully developed organ, the placenta provides nutrition and excretion, respiration, and endocrine function. It receives blood from the fetus through the umbilical arteries. Capillaries in the chorionic villi filter fetal wastes out of the blood and return clean, oxygenated blood to the fetus through the umbilical vein. Nutrients and oxygen are transferred from maternal blood surrounding the villi through the capillaries and into the fetal bloodstream. Some substances move across the placenta by simple diffusion. Oxygen, carbon dioxide, and any other lipid-soluble substances take this route. Other substances move across by facilitated diffusion. This includes water-soluble glucose. The fetus has a high demand for amino acids and iron, and those substances are moved across the placenta by active transport.

Maternal and fetal blood does not commingle because blood cells cannot move across the placenta. This separation prevents the mother’s cytotoxic T cells from reaching and subsequently destroying the fetus, which bears “non-self” antigens. Further, it ensures the fetal red blood cells do not enter the mother’s circulation and trigger antibody development (if they carry “non-self” antigens)—at least until the final stages of pregnancy or birth. This is the reason that, even in the absence of preventive treatment, an Rh⁻ mother doesn’t develop antibodies that could cause hemolytic disease in her first Rh⁺ fetus.

Although blood cells are not exchanged, the chorionic villi provide ample surface area for the two-way exchange of substances between maternal and fetal blood. The rate of exchange increases throughout gestation as the villi become thinner and increasingly branched. The placenta is permeable to lipid-soluble fetotoxic substances: alcohol, nicotine, barbiturates, antibiotics, certain pathogens, and many other substances that can be dangerous or fatal to the developing embryo or fetus. For these reasons, pregnant women should avoid fetotoxic substances. Alcohol consumption by pregnant women, for example, can result in a range of abnormalities referred to as fetal alcohol spectrum disorders (FASD). These include organ and facial malformations, as well as cognitive and behavioral disorders.

The development of multi-cellular organisms begins from a single-celled zygote, which undergoes rapid cell division to form the blastula. The rapid, multiple rounds of cell division are termed cleavage. Cleavage is illustrated in (Figure 43.24a). After the cleavage has produced over 100 cells, the embryo is called a blastula. The blastula is usually a spherical layer of cells (the blastoderm) surrounding a fluid-filled or yolk-filled cavity (the blastocoel). Mammals at this stage form a structure called the blastocyst, characterized by an inner cell mass that is distinct from the surrounding blastula, shown in Figure 43.24b. During cleavage, the cells divide without an increase in mass; that is, one large single-celled zygote divides into multiple smaller cells. Each cell within the blastula is called a blastomere.

Figure 43.24 (a) During cleavage, the zygote rapidly divides into multiple cells without increasing in size. (b) The cells rearrange themselves to form a hollow ball with a fluid-filled or yolk-filled cavity called the blastula.

Cleavage can take place in two ways: holoblastic (total) cleavage or meroblastic (partial) cleavage. The type of cleavage depends on the amount of yolk in the eggs. In placental mammals (including humans) where nourishment is provided by the parent’s body, the eggs have a very small amount of yolk and undergo holoblastic cleavage. Other species, such as birds, with a lot of yolk in the egg to nourish the embryo during development, undergo meroblastic cleavage.

In mammals, the blastula forms the blastocyst in the next stage of development. Here the cells in the blastula arrange themselves in two layers: the inner cell mass, and an outer layer called the trophoblast. The inner cell mass is also known as the embryoblast and this mass of cells will go on to form the embryo. At this stage of development, illustrated in Figure 43.25 the inner cell mass consists of embryonic stem cells that will differentiate into the different cell types needed by the organism. The trophoblast will contribute to the placenta and nourish the embryo.

Figure 43.25 The rearrangement of the cells in the mammalian blastula to two layers—the inner cell mass and the trophoblast—results in the formation of the blastocyst.

Contact Between Sperm and Oocyte

Upon ovulation, the oocyte released by the ovary is swept into-and along-the uterine tube. Fertilization must occur in the distal uterine tube because an unfertilized oocyte cannot survive the 72-hour journey to the uterus. As you will recall from your study of the oogenesis, this oocyte (specifically a secondary oocyte) is surrounded by two protective layers. The corona radiata is an outer layer of follicular (granulosa) cells that form around a developing oocyte in the ovary and remain with it upon ovulation. The underlying zona pellucida (pellucid = "transparent") is a transparent, but thick, glycoprotein membrane that surrounds the cell's plasma membrane.

As it is swept along the distal uterine tube, the oocyte encounters the surviving capacitated sperm, which stream toward it in response to chemical attractants released by the cells of the corona radiata. To reach the oocyte itself, the sperm must penetrate the two protective layers. The sperm first burrow through the cells of the corona radiata. Then, upon contact with the zona pellucida, the sperm bind to receptors in the zona pellucida. This initiates a process called the acrosomal reaction in which the enzyme-filled "cap" of the sperm, called the acrosome, releases its stored digestive enzymes. These enzymes clear a path through the zona pellucida that allows sperm to reach the oocyte. Finally, a single sperm makes contact with sperm-binding receptors on the oocyte's plasma membrane (Figure). The plasma membrane of that sperm then fuses with the oocyte's plasma membrane, and the head and mid-piece of the "winning" sperm enter the oocyte interior.

How do sperm penetrate the corona radiata? Some sperm undergo a spontaneous acrosomal reaction, which is an acrosomal reaction not triggered by contact with the zona pellucida. The digestive enzymes released by this reaction digest the extracellular matrix of the corona radiata. As you can see, the first sperm to reach the oocyte is never the one to fertilize it. Rather, hundreds of sperm cells must undergo the acrosomal reaction, each helping to degrade the corona radiata and zona pellucida until a path is created to allow one sperm to contact and fuse with the plasma membrane of the oocyte. If you consider the loss of millions of sperm between entry into the vagina and degradation of the zona pellucida, you can understand why a low sperm count can cause male infertility.

Sperm and the Process of Fertilization

Before fertilization, hundreds of capacitated sperm must break through the surrounding corona radiata and zona pellucida so that one can contact and fuse with the oocyte plasma membrane.

Corpus Luteum is the endocrine tissue that develops from an ovarian follicle after ovulation; secretes progesterone and estrogen during pregnancy.

Human beta chorionic gonadotropin (β-HCG) is a hormone produced by the chorion of the zygote that helps to maintain the corpus luteum and elevated levels of progesterone.

Ovarian cycle the cycle of preparation of egg for ovulation and the conversion of the follicle to the corpus luteum.

Internal female reproductive structures include ovaries, oviducts, the uterus, and the vagina (Figure; Table). The pair of ovaries is held in place in the abdominal cavity by a system of ligaments. The outermost layer of the ovary is made up of follicles, each consisting of one or more follicular cells that surround, nourish, and protect a single egg. During the menstrual period, a batch of follicular cells develops and prepares their eggs for release. At ovulation, one follicle ruptures and one egg is released. Following ovulation, the follicular tissue that surrounded the ovulated egg stays within the ovary and grows to form a solid mass called the corpus luteum. The corpus luteum secretes additional estrogen and the hormone progesterone that helps maintain the uterine lining during pregnancy. The ovaries also produce hormones, such as estrogen.

ART CONNECTION

Just prior to the middle of the cycle (approximately day 14), the high level of estrogen causes FSH and especially LH to rise rapidly then fall. The spike in LH causes the most mature follicle to rupture and release its egg. This is ovulation. The follicles that did not rupture degenerate and their eggs are lost. The level of estrogen decreases when the extra follicles degenerate.

Following ovulation, the ovarian cycle enters its luteal phase and the menstrual cycle enters its secretory phase, both of which run from about day 15 to 28. The luteal and secretory phases refer to changes in the ruptured follicle. The cells in the follicle undergo physical changes and produce a structure called a corpus luteum. The corpus luteum produces estrogen and progesterone. The progesterone facilitates the regrowth of the uterine lining and inhibits the release of further FSH and LH. The uterus is being prepared to accept a fertilized egg, should it occur during this cycle. The inhibition of FSH and LH prevents any further eggs and follicles from developing, while the progesterone is elevated. The level of estrogen produced by the corpus luteum increases to a steady level for the next few days.

If no fertilized egg is implanted into the uterus, the corpus luteum degenerates and the levels of estrogen and progesterone decrease. The endometrium begins to degenerate as the progesterone levels drop, initiating the next menstrual cycle. The decrease in progesterone also allows the hypothalamus to send GnRH to the anterior pituitary, releasing FSH and LH and starting the cycles again.

Implantation is the process by which a blastocyst embeds itself in the uterine endometrium

At the end of the first week, the blastocyst comes in contact with the uterine wall and adheres to it, embedding itself in the uterine lining via the trophoblast cells. Thus begins the process of implantation, which signals the end of the pre-embryonic stage of development (Figure). Implantation can be accompanied by minor bleeding. The blastocyst typically implants in the fundus of the uterus or on the posterior wall. However, if the endometrium is not fully developed and ready to receive the blastocyst, the blastocyst will detach and find a better spot. A significant percentage (50-75 percent) of blastocysts fail to implant; when this occurs, the blastocyst is shed with the endometrium during menses. The high rate of implantation failure is one reason why pregnancy typically requires several ovulation cycles to achieve.

Pre-Embryonic Development

Figure 28.5 Pre-Embryonic Development Ovulation, fertilization, pre-embryonic development, and implantation occur at specific locations within the female reproductive system in a time span of approximately 1 week.

Ovulation, fertilization, pre-embryonic development, and implantation occur at specific locations within the female reproductive system in a time span of approximately 1 week.

When implantation succeeds and the blastocyst adheres to the endometrium, the superficial cells of the trophoblast fuse with each other, forming the syncytiotrophoblast, a multinucleated body that digests endometrial cells to firmly secure the blastocyst to the uterine wall. In response, the uterine mucosa rebuilds itself and envelops the blastocyst (Figure). The trophoblast secretes human chorionic gonadotropin (hCG), a hormone that directs the corpus luteum to survive, enlarge, and continue producing progesterone and estrogen to suppress menses. These functions of hCG are necessary for creating an environment suitable for the developing embryo. As a result of this increased production, hCG accumulates in the maternal bloodstream and is excreted in the urine. Implantation is complete by the middle of the second week. Just a few days after implantation, the trophoblast has secreted enough hCG for an at-home urine pregnancy test to give a positive result.

Implantation

During implantation, the trophoblast cells of the blastocyst adhere to the endometrium and digest endometrial cells until it is attached securely.

Figure 28.6 Implantation During implantation, the trophoblast cells of the blastocyst adhere to the endometrium and digest endometrial cells until it is attached securely.

Most of the time an embryo implants within the body of the uterus in a location that can support growth and development. However, in one to two percent of cases, the embryo implants either outside the uterus (an ectopic pregnancy) or in a region of uterus that can create complications for the pregnancy. If the embryo implants in the inferior portion of the uterus, the placenta can potentially grow over the opening of the cervix, a condition call placenta previa.

Inner lining of the uterus, part of which builds up during the secretory phase of the menstrual cycle and then sheds with menses.

The innermost layer of the uterus is called the endometrium. The endometrium contains a connective tissue lining, the lamina propria, which is covered by epithelial tissue that lines the lumen. Structurally, the endometrium consists of two layers: the stratum basalis and the stratum functionalis (the basal and functional layers). The stratum basalis layer is part of the lamina propria and is adjacent to the myometrium; this layer does not shed during menses. In contrast, the thicker stratum functionalis layer contains the glandular portion of the lamina propria and the endothelial tissue that lines the uterine lumen. It is the stratum functionalis that grows and thickens in response to increased levels of estrogen and progesterone. In the luteal phase of the menstrual cycle, special branches off of the uterine artery called spiral arteries supply the thickened stratum functionalis. This inner functional layer provides the proper site of implantation for the fertilized egg, and—should fertilization not occur—it is only the stratum functionalis layer of the endometrium that sheds during menstruation.

Recall that during the follicular phase of the ovarian cycle, the tertiary follicles are growing and secreting estrogen. At the same time, the stratum functionalis of the endometrium is thickening to prepare for a potential implantation. The post-ovulatory increase in progesterone, which characterizes the luteal phase, is key for maintaining a thick stratum functionalis. As long as a functional corpus luteum is present in the ovary, the endometrial lining is prepared for implantation. Indeed, if an embryo implants, signals are sent to the corpus luteum to continue secreting progesterone to maintain the endometrium, and thus maintain the pregnancy. If an embryo does not implant, no signal is sent to the corpus luteum and it degrades, ceasing progesterone production and ending the luteal phase. Without progesterone, the endometrium thins and, under the influence of prostaglandins, the spiral arteries of the endometrium constrict and rupture, preventing oxygenated blood from reaching the endometrial tissue. As a result, endometrial tissue dies and blood, pieces of the endometrial tissue, and white blood cells are shed through the vagina during menstruation, or the menses. The first menses after puberty, called menarche, can occur either before or after the first ovulation.

Ovaries, Uterine Tubes, and Uterus

This anterior view shows the relationship of the ovaries, uterine tubes (oviducts), and uterus. Sperm enter through the vagina, and fertilization of an ovulated oocyte usually occurs in the distal uterine tube. From left to right, LM × 400, LM × 20. (Micrographs provided by the Regents of University of Michigan Medical School © 2012)

The primary hormones produced by the ovaries are estrogens, which include estradiol, estriol, and estrone. Estrogens play an important role in a larger number of physiological processes, including the development of the female reproductive system, regulation of the menstrual cycle, the development of female secondary sex characteristics such as increased adipose tissue and the development of breast tissue, and the maintenance of pregnancy. Another significant ovarian hormone is progesterone, which contributes to regulation of the menstrual cycle and is important in preparing the body for pregnancy as well as maintaining pregnancy. In addition, the granulosa cells of the ovarian follicles produce inhibin, which—as in males—inhibits the secretion of FSH.During the initial stages of pregnancy, an organ called the placenta develops within the uterus. The placenta supplies oxygen and nutrients to the fetus, excretes waste products, and produces and secretes estrogens and progesterone. The placenta produces human chorionic gonadotropin (hCG) as well. The hCG hormone promotes progesterone synthesis and reduces the mother’s immune function to protect the fetus from immune rejection. It also secretes human placental lactogen (hPL), which plays a role in preparing the breasts for lactation, and relaxin, which is thought to help soften and widen the pubic symphysis in preparation for childbirth. The hormones controlling reproduction are summarized in Table.

Follicle-stimulating hormone is a reproductive hormone that causes sperm production in men and follicle development in women.

The human male and female reproductive cycles are controlled by the interaction of hormones from the hypothalamus and anterior pituitary with hormones from reproductive tissues and organs. In both sexes, the hypothalamus monitors and causes the release of hormones from the pituitary gland. When the reproductive hormone is required, the hypothalamus sends a gonadotropin-releasing hormone (GnRH) to the anterior pituitary. This causes the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary into the blood. Note that the body must reach puberty in order for the adrenals to release the hormones that must be present for GnRH to be produced. Although FSH and LH are named after their functions in female reproduction, they are produced in both sexes and play important roles in controlling reproduction. Other hormones have specific functions in the male and female reproductive systems.

Female Hormones

The control of reproduction in females is more complex. As with the male, the anterior pituitary hormones cause the release of the hormones FSH and LH. In addition, estrogens and progesterone are released from the developing follicles. Estrogen is the reproductive hormone in females that assists in endometrial regrowth, ovulation, and calcium absorption; it is also responsible for the secondary sexual characteristics of females. These include breast development, flaring of the hips, and a shorter period necessary for bone maturation. Progesterone assists in endometrial re-growth and inhibition of FSH and LH release.

In females, FSH stimulates development of egg cells, called ova, which develop in structures called follicles. Follicle cells produce the hormone inhibin, which inhibits FSH production. LH also plays a role in the development of ova, induction of ovulation, and stimulation of estradiol and progesterone production by the ovaries. Estradiol and progesterone are steroid hormones that prepare the body for pregnancy. Estradiol produces secondary sex characteristics in females, while both estradiol and progesterone regulate the menstrual cycle.

The Ovarian Cycle and the Menstrual Cycle

The ovarian cycle governs the preparation of endocrine tissues and release of eggs, while the menstrual cycle governs the preparation and maintenance of the uterine lining. These cycles occur concurrently and are coordinated over a 22–32 day cycle, with an average length of 28 days.

The first half of the ovarian cycle is the follicular phase shown in Figure. Slowly rising levels of FSH and LH cause the growth of follicles on the surface of the ovary. This process prepares the egg for ovulation. As the follicles grow, they begin releasing estrogens and a low level of progesterone. Progesterone maintains the endometrium to help ensure pregnancy. The trip through the fallopian tube takes about seven days. At this stage of development, called the morula, there are 30-60 cells. If pregnancy implantation does not occur, the lining is sloughed off. After about five days, estrogen levels rise and the menstrual cycle enters the proliferative phase. The endometrium begins to regrow, replacing the blood vessels and glands that deteriorated during the end of the last cycle.

ART CONNECTION

Just prior to the middle of the cycle (approximately day 14), the high level of estrogen causes FSH and especially LH to rise rapidly, then fall. The spike in LH causes ovulation: the most mature follicle, like that shown in Figure, ruptures and releases its egg. The follicles that did not rupture degenerate and their eggs are lost. The level of estrogen decreases when the extra follicles degenerate.

Following ovulation, the ovarian cycle enters its luteal phase, illustrated in Figure and the menstrual cycle enters its secretory phase, both of which run from about day 15 to 28. The luteal and secretory phases refer to changes in the ruptured follicle. The cells in the follicle undergo physical changes and produce a structure called a corpus luteum. The corpus luteum produces estrogen and progesterone. The progesterone facilitates the regrowth of the uterine lining and inhibits the release of further FSH and LH. The uterus is being prepared to accept a fertilized egg, should it occur during this cycle. The inhibition of FSH and LH prevents any further eggs and follicles from developing, while the progesterone is elevated. The level of estrogen produced by the corpus luteum increases to a steady level for the next few days.

If no fertilized egg is implanted into the uterus, the corpus luteum degenerates and the levels of estrogen and progesterone decrease. The endometrium begins to degenerate as the progesterone levels drop, initiating the next menstrual cycle. The decrease in progesterone also allows the hypothalamus to send GnRH to the anterior pituitary, releasing FSH and LH and starting the cycles again. Figure visually compares the ovarian and uterine cycles as well as the commensurate hormone levels.

ART CONNECTION

Summary

The male and female reproductive cycles are controlled by hormones released from the hypothalamus and anterior pituitary as well as hormones from reproductive tissues and organs. The hypothalamus monitors the need for the FSH and LH hormones made and released from the anterior pituitary. FSH and LH affect reproductive structures to cause the formation of sperm and the preparation of eggs for release and possible fertilization. In the male, FSH and LH stimulate Sertoli cells and interstitial cells of Leydig in the testes to facilitate sperm production. The Leydig cells produce testosterone, which also is responsible for the secondary sexual characteristics of males. In females, FSH and LH cause estrogen and progesterone to be produced. They regulate the female reproductive system which is divided into the ovarian cycle and the menstrual cycle. Menopause occurs when the ovaries lose their sensitivity to FSH and LH and the female reproductive cycles slow to a stop.

Folliculogenesis is the development of ovarian follicles from primordial to tertiary under the stimulation of gonadotropins.

Ovarian follicles are oocytes and their supporting cells. They grow and develop in a process called folliculogenesis, which typically leads to ovulation of one follicle approximately every 28 days, along with death to multiple other follicles. The death of ovarian follicles is called atresia, and can occur at any point during follicular development. Recall that, a female infant at birth will have one to two million oocytes within her ovarian follicles, and that this number declines throughout life until menopause, when no follicles remain. As you'll see next, follicles progress from primordial, to primary, to secondary and tertiary stages prior to ovulation-with the oocyte inside the follicle remaining as a primary oocyte until right before ovulation.

Folliculogenesis begins with follicles in a resting state. These small primordial follicles are present in newborn females and are the prevailing follicle type in the adult ovary (Figure). Primordial follicles have only a single flat layer of support cells, called granulosa cells, that surround the oocyte, and they can stay in this resting state for years-some until right before menopause.After puberty, a few primordial follicles will respond to a recruitment signal each day, and will join a pool of immature growing follicles called primary follicles. Primary follicles start with a single layer of granulosa cells, but the granulosa cells then become active and transition from a flat or squamous shape to a rounded, cuboidal shape as they increase in size and proliferate. As the granulosa cells divide, the follicles-now called secondary follicles (see Figure)-increase in diameter, adding a new outer layer of connective tissue, blood vessels, and theca cells-cells that work with the granulosa cells to produce estrogens.

Within the growing secondary follicle, the primary oocyte now secretes a thin acellular membrane called the zona pellucida that will play a critical role in fertilization. A thick fluid, called follicular fluid, that has formed between the granulosa cells also begins to collect into one large pool, or antrum. Follicles in which the antrum has become large and fully formed are considered tertiary follicles (or antral follicles). Several follicles reach the tertiary stage at the same time, and most of these will undergo atresia. The one that does not die will continue to grow and develop until ovulation, when it will expel its secondary oocyte surrounded by several layers of granulosa cells from the ovary. Keep in mind that most follicles don't make it to this point. In fact, roughly 99 percent of the follicles in the ovary will undergo atresia, which can occur at any stage of folliculogenesis.

Folliculogenesis

(a) The maturation of a follicle is shown in a clockwise direction proceeding from the primordial follicles. FSH stimulates the growth of a tertiary follicle, and LH stimulates the production of estrogen by granulosa and theca cells. Once the follicle is mature, it ruptures and releases the oocyte. Cells remaining in the follicle then develop into the corpus luteum. (b) In this electron micrograph of a secondary follicle, the oocyte, theca cells (thecae folliculi), and developing antrum are clearly visible. EM × 1100. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)

Gamete is a haploid reproductive cell that contributes genetic material to form an offspring.

Unique for its role in human reproduction, a gamete is a specialized sex cell carrying 23 chromosomes—one half the number in body cells. At fertilization, the chromosomes in one male gamete, called a sperm (or spermatozoon), combine with the chromosomes in one female gamete, called an oocyte. The function of the male reproductive system (Figure) is to produce sperm and transfer them to the female reproductive tract. The paired testes are a crucial component in this process, as they produce both sperm and androgens, the hormones that support male reproductive physiology. In humans, the most important male androgen is testosterone. Several accessory organs and ducts aid the process of sperm maturation and transport the sperm and other seminal components to the penis, which delivers sperm to the female reproductive tract. In this section, we examine each of these different structures, and discuss the process of sperm production and transport.

The process of spermatogenesis begins with mitosis of the diploid spermatogonia (Figure). Because these cells are diploid (2n), they each have a complete copy of the father’s genetic material, or 46 chromosomes. However, mature gametes are haploid (1n), containing 23 chromosomes—meaning that daughter cells of spermatogonia must undergo a second cellular division through the process of meiosis.

Gastrulation is a process in which the blastula folds over itself to form the three germ layers.

The typical blastula is a ball of cells. The next stage in embryonic development is the formation of the body plan. The cells in the blastula rearrange themselves spatially to form three layers of cells. This process is called gastrulation. During gastrulation, the blastula folds upon itself to form the three layers of cells. Each of these layers is called a germ layer and each germ layer differentiates into different organ systems.

The three germs layers, shown in Figure, are the endoderm, the ectoderm, and the mesoderm. The ectoderm gives rise to the nervous system and the epidermis. The mesoderm gives rise to the muscle cells and connective tissue in the body. The endoderm gives rise to columnar cells found in the digestive system and many internal organs.

Gonadotropin-releasing hormone is a hormone made by a part of the brain called the hypothalamus. Gonadotropin-releasing hormone causes the pituitary gland in the brain to make and secrete the hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In men, these hormones cause the testicles to make testosterone. In women, they cause the ovaries to make estrogen and progesterone. Also called GnRH, LH-RH, LHRH, and luteinizing hormone-releasing hormone.

Luteinizing Hormone (LH) is a reproductive hormone in both men and women, causes testosterone production in men and ovulation and lactation in women.

Hormonal Control of Reproduction

The human male and female reproductive cycles are controlled by the interaction of hormones from the hypothalamus and anterior pituitary with hormones from reproductive tissues and organs. In both sexes, the hypothalamus monitors and causes the release of hormones from the anterior pituitary gland. When the reproductive hormone is required, the hypothalamus sends a gonadotropin-releasing hormone (GnRH) to the anterior pituitary. This causes the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary into the blood. Although these hormones are named after their functions in female reproduction, they are produced in both sexes and play important roles in controlling reproduction. Other hormones have specific functions in the male and female reproductive systems.

Hormones control sperm production in a negative feedback system.



The ovarian and menstrual cycles of female reproduction are regulated by hormones produced by the hypothalamus, pituitary, and ovaries.

A morula is a tightly packed sphere of blastomeres that has reached the uterus but has not yet implanted itself.

Approximately 3 days after fertilization, a 16-cell conceptus reaches the uterus. The cells that had been loosely grouped are now compacted and look more like a solid mass. The name given to this structure is the morula (morula = “little mulberry”). Once inside the uterus, the conceptus floats freely for several more days. It continues to divide, creating a ball of approximately 100 cells, and consuming nutritive endometrial secretions called uterine milk while the uterine lining thickens. The ball of now tightly bound cells starts to secrete fluid and organize themselves around a fluid-filled cavity, the blastocoel. At this developmental stage, the conceptus is referred to as a blastocyst. Within this structure, a group of cells forms into an inner cell mass, which is fated to become the embryo. The cells that form the outer shell are called trophoblasts (trophe = “to feed” or “to nourish”). These cells will develop into the chorionic sac and the fetal portion of the placenta (the organ of nutrient, waste, and gas exchange between mother and the developing offspring).

Pre-Embryonic Cleavages

Pre-embryonic cleavages make use of the abundant cytoplasm of the conceptus as the cells rapidly divide without changing the total volume.

Pre-Embryonic Development

Ovulation, fertilization, pre-embryonic development, and implantation occur at specific locations within the female reproductive system in a time span of approximately 1 week.

oocyte

cell that results from the division of the oogonium and undergoes meiosis I at the LH surge and meiosis II at fertilization to become a haploid ovum

oogenesis

process by which oogonia divide by mitosis to primary oocytes, which undergo meiosis to produce the secondary oocyte and, upon fertilization, the ovum

oogonia

ovarian stem cells that undergo mitosis during female fetal development to form primary oocytes

The Ovarian Cycle

The ovarian cycle is a set of predictable changes in a female’s oocytes and ovarian follicles. During a woman’s reproductive years, it is a roughly 28-day cycle that can be correlated with, but is not the same as, the menstrual cycle (discussed shortly). The cycle includes two interrelated processes: oogenesis (the production of female gametes) and folliculogenesis (the growth and development of ovarian follicles).

Oogenesis

Gametogenesis in females is called oogenesis. The process begins with the ovarian stem cells, or oogonia (Figure). Oogonia are formed during fetal development, and divide via mitosis, much like spermatogonia in the testis. Unlike spermatogonia, however, oogonia form primary oocytes in the fetal ovary prior to birth. These primary oocytes are then arrested in this stage of meiosis I, only to resume it years later, beginning at puberty and continuing until the woman is near menopause (the cessation of a woman’s reproductive functions). The number of primary oocytes present in the ovaries declines from one to two million in an infant, to approximately 400,000 at puberty, to zero by the end of menopause.

The initiation of ovulation—the release of an oocyte from the ovary—marks the transition from puberty into reproductive maturity for women. From then on, throughout a woman’s reproductive years, ovulation occurs approximately once every 28 days. Just prior to ovulation, a surge of luteinizing hormone triggers the resumption of meiosis in a primary oocyte. This initiates the transition from primary to secondary oocyte. However, as you can see in Figure, this cell division does not result in two identical cells. Instead, the cytoplasm is divided unequally, and one daughter cell is much larger than the other. This larger cell, the secondary oocyte, eventually leaves the ovary during ovulation. The smaller cell, called the first polar body, may or may not complete meiosis and produce second polar bodies; in either case, it eventually disintegrates. Therefore, even though oogenesis produces up to four cells, only one survives.

How does the diploid secondary oocyte become an ovum—the haploid female gamete? Meiosis of a secondary oocyte is completed only if a sperm succeeds in penetrating its barriers. Meiosis II then resumes, producing one haploid ovum that, at the instant of fertilization by a (haploid) sperm, becomes the first diploid cell of the new offspring (a zygote). Thus, the ovum can be thought of as a brief, transitional, haploid stage between the diploid oocyte and diploid zygote.

The larger amount of cytoplasm contained in the female gamete is used to supply the developing zygote with nutrients during the period between fertilization and implantation into the uterus. Interestingly, sperm contribute only DNA at fertilization —not cytoplasm. Therefore, the cytoplasm and all of the cytoplasmic organelles in the developing embryo are of maternal origin. This includes mitochondria, which contain their own DNA. Scientific research in the 1980s determined that mitochondrial DNA was maternally inherited, meaning that you can trace your mitochondrial DNA directly to your mother, her mother, and so on back through your female ancestors.

Review

The ovaries produce oocytes, the female gametes, in a process called oogenesis. As with spermatogenesis, meiosis produces the haploid gamete (in this case, an ovum); however, it is completed only in an oocyte that has been penetrated by a sperm. In the ovary, an oocyte surrounded by supporting cells is called a follicle. In folliculogenesis, primordial follicles develop into primary, secondary, and tertiary follicles. Early tertiary follicles with their fluid-filled antrum will be stimulated by an increase in FSH, a gonadotropin produced by the anterior pituitary, to grow in the 28-day ovarian cycle. Supporting granulosa and theca cells in the growing follicles produce estrogens, until the level of estrogen in the bloodstream is high enough that it triggers negative feedback at the hypothalamus and pituitary. This results in a reduction of FSH and LH, and most tertiary follicles in the ovary undergo atresia (they die). One follicle, usually the one with the most FSH receptors, survives this period and is now called the dominant follicle. The dominant follicle produces more estrogen, triggering positive feedback and the LH surge that will induce ovulation. Following ovulation, the granulosa cells of the empty follicle luteinize and transform into the progesterone-producing corpus luteum. The ovulated oocyte with its surrounding granulosa cells is picked up by the infundibulum of the uterine tube, and beating cilia help to transport it through the tube toward the uterus. Fertilization occurs within the uterine tube, and the final stage of meiosis is completed.

Gametogenesis in females is called oogenesis. The process begins with the ovarian stem cells, or oogonia (Figure). Oogonia are formed during fetal development, and divide via mitosis, much like spermatogonia in the testis. Unlike spermatogonia, however, oogonia form primary oocytes in the fetal ovary prior to birth. These primary oocytes are then arrested in this stage of meiosis I, only to resume it years later, beginning at puberty and continuing until the woman is near menopause (the cessation of a woman's reproductive functions). The number of primary oocytes present in the ovaries declines from one to two million in an infant, to approximately 400,000 at puberty, to zero by the end of menopause.

The initiation of ovulation-the release of an oocyte from the ovary-marks the transition from puberty into reproductive maturity for women. From then on, throughout a woman's reproductive years, ovulation occurs approximately once every 28 days. Just prior to ovulation, a surge of luteinizing hormone triggers the resumption of meiosis in a primary oocyte. This initiates the transition from primary to secondary oocyte. However, as you can see in Figure, this cell division does not result in two identical cells. Instead, the cytoplasm is divided unequally, and one daughter cell is much larger than the other. This larger cell, the secondary oocyte, eventually leaves the ovary during ovulation. The smaller cell, called the first polar body, may or may not complete meiosis and produce second polar bodies; in either case, it eventually disintegrates. Therefore, even though oogenesis produces up to four cells, only one survives.

Oogenesis

The unequal cell division of oogenesis produces one to three polar bodies that later degrade, as well as a single haploid ovum, which is produced only if there is penetration of the secondary oocyte by a sperm cell.

How does the diploid secondary oocyte become an ovum-the haploid female gamete? Meiosis of a secondary oocyte is completed only if a sperm succeeds in penetrating its barriers. Meiosis II then resumes, producing one haploid ovum that, at the instant of fertilization by a (haploid) sperm, becomes the first diploid cell of the new offspring (a zygote). Thus, the ovum can be thought of as a brief, transitional, haploid stage between the diploid oocyte and diploid zygote.

The larger amount of cytoplasm contained in the female gamete is used to supply the developing zygote with nutrients during the period between fertilization and implantation into the uterus. Interestingly, sperm contribute only DNA at fertilization -not cytoplasm. Therefore, the cytoplasm and all of the cytoplasmic organelles in the developing embryo are of maternal origin. This includes mitochondria, which contain their own DNA. Scientific research in the 1980s determined that mitochondrial DNA was maternally inherited, meaning that you can trace your mitochondrial DNA directly to your mother, her mother, and so on back through your female ancestors.

Ovulation is the release of the egg by the most mature follicle.

Female Hormones

The control of reproduction in females is more complex. As with the male, the anterior pituitary hormones cause the release of the hormones FSH and LH. In addition, estrogens and progesterone are released from the developing follicles. Estrogen is the reproductive hormone in females that assists in endometrial regrowth, ovulation, and calcium absorption; it is also responsible for the secondary sexual characteristics of females. These include breast development, flaring of the hips, and a shorter period necessary for bone maturation. Progesterone assists in endometrial re-growth and inhibition of FSH and LH release.

In females, FSH stimulates development of egg cells, called ova, which develop in structures called follicles. Follicle cells produce the hormone inhibin, which inhibits FSH production. LH also plays a role in the development of ova, induction of ovulation, and stimulation of estradiol and progesterone production by the ovaries. Estradiol and progesterone are steroid hormones that prepare the body for pregnancy. Estradiol produces secondary sex characteristics in females, while both estradiol and progesterone regulate the menstrual cycle.

The Ovarian Cycle and the Menstrual Cycle

The ovarian cycle governs the preparation of endocrine tissues and release of eggs, while the menstrual cycle governs the preparation and maintenance of the uterine lining. These cycles occur concurrently and are coordinated over a 22–32 day cycle, with an average length of 28 days.

The first half of the ovarian cycle is the follicular phase shown in the Figure below. Slowly rising levels of FSH and LH cause the growth of follicles on the surface of the ovary. This process prepares the egg for ovulation. As the follicles grow, they begin releasing estrogens and a low level of progesterone. Progesterone maintains the endometrium to help ensure pregnancy. The trip through the fallopian tube takes about seven days. At this stage of development, called the morula, there are 30-60 cells. If pregnancy implantation does not occur, the lining is sloughed off. After about five days, estrogen levels rise and the menstrual cycle enters the proliferative phase. The endometrium begins to regrow, replacing the blood vessels and glands that deteriorated during the end of the last cycle.

The ovarian and menstrual cycles of female reproduction are regulated by hormones produced by the hypothalamus, pituitary, and ovaries.

Just prior to the middle of the cycle (approximately day 14), the high level of estrogen causes FSH and especially LH to rise rapidly, then fall. The spike in LH causes ovulation: the most mature follicle, like that shown in Figure, ruptures and releases its egg. The follicles that did not rupture degenerate and their eggs are lost. The level of estrogen decreases when the extra follicles degenerate.

Following ovulation, the ovarian cycle enters its luteal phase, and the menstrual cycle enters its secretory phase, both of which run from about day 15 to 28. The luteal and secretory phases refer to changes in the ruptured follicle. The cells in the follicle undergo physical changes and produce a structure called a corpus luteum. The corpus luteum produces estrogen and progesterone. The progesterone facilitates the regrowth of the uterine lining and inhibits the release of further FSH and LH. The uterus is being prepared to accept a fertilized egg, should it occur during this cycle. The inhibition of FSH and LH prevents any further eggs and follicles from developing, while the progesterone is elevated. The level of estrogen produced by the corpus luteum increases to a steady level for the next few days.

If no fertilized egg is implanted into the uterus, the corpus luteum degenerates and the levels of estrogen and progesterone decrease. The endometrium begins to degenerate as the progesterone levels drop, initiating the next menstrual cycle. The decrease in progesterone also allows the hypothalamus to send GnRH to the anterior pituitary, releasing FSH and LH and starting the cycles again. Figure above visually compares the ovarian and uterine cycles as well as the commensurate hormone levels.

Ovum is a haploid female gamete resulting from completion of meiosis II at fertilization.

Oogenesis

The unequal cell division of oogenesis produces one to three polar bodies that later degrade, as well as a single haploid ovum, which is produced only if there is penetration of the secondary oocyte by a sperm cell.

How does the diploid secondary oocyte become an ovum—the haploid female gamete? Meiosis of a secondary oocyte is completed only if a sperm succeeds in penetrating its barriers. Meiosis II then resumes, producing one haploid ovum that, at the instant of fertilization by a (haploid) sperm, becomes the first diploid cell of the new offspring (a zygote). Thus, the ovum can be thought of as a brief, transitional, haploid stage between the diploid oocyte and diploid zygote.

The larger amount of cytoplasm contained in the female gamete is used to supply the developing zygote with nutrients during the period between fertilization and implantation into the uterus. Interestingly, sperm contribute only DNA at fertilization —not cytoplasm. Therefore, the cytoplasm and all of the cytoplasmic organelles in the developing embryo are of maternal origin. This includes mitochondria, which contain their own DNA. Scientific research in the 1980s determined that mitochondrial DNA was maternally inherited, meaning that you can trace your mitochondrial DNA directly to your mother, her mother, and so on back through your female ancestors.

Review

The ovaries produce oocytes, the female gametes, in a process called oogenesis. As with spermatogenesis, meiosis produces the haploid gamete (in this case, an ovum); however, it is completed only in an oocyte that has been penetrated by a sperm. In the ovary, an oocyte surrounded by supporting cells is called a follicle. In folliculogenesis, primordial follicles develop into primary, secondary, and tertiary follicles. The ovulated oocyte with its surrounding granulosa cells is picked up by the infundibulum of the uterine tube, and beating cilia help to transport it through the tube toward the uterus. Fertilization occurs within the uterine tube, and the final stage of meiosis is completed.

The placenta is an organ that supports the diffusion of nutrients and waste between the mother’s and fetus’ blood.

The gestation period is divided into three equal periods or trimesters. During the first two to four weeks of the first trimester, nutrition and waste are handled by the endometrial lining through diffusion. As the trimester progresses, the outer layer of the embryo begins to merge with the endometrium, and the placenta forms. This organ takes over the nutrient and waste requirements of the embryo and fetus, with the parent’s blood passing nutrients to the placenta and removing waste from it. Chemicals from the fetus, such as bilirubin, are processed by the parent’s liver for elimination. Some of the parent’s immunoglobulins will pass through the placenta, providing passive immunity against some potential infections.

Internal organs and body structures begin to develop during the first trimester. By five weeks, limb buds, eyes, the heart, and liver have been basically formed. By eight weeks, the term fetus applies, and the body is essentially formed, as shown in Figure 43.19. The individual is about five centimeters (two inches) in length and many of the organs, such as the lungs and liver, are not yet functioning. Exposure to any toxins is especially dangerous during the first trimester, as all of the body’s organs and structures are going through initial development. Anything that affects that development can have a severe effect on the fetus’ survival.

During the second trimester, the fetus grows to about 30 cm (12 inches), as shown in Figure 43.20. It becomes active and the pregnant person usually feels the first movements. All organs and structures continue to develop. The placenta has taken over the functions of nutrition and waste and the production of estrogen and progesterone from the corpus luteum, which has degenerated. The placenta will continue functioning up through the delivery of the baby.

During the third trimester, the fetus grows to 3 to 4 kg (6 ½ -8 ½ lbs.) and about 50 cm (19-20 inches) long, as illustrated in Figure 43.21. This is the period of the most rapid growth during the pregnancy. Organ development continues to birth (and some systems, such as the nervous system and liver, continue to develop after birth). The pregnant person will be most uncomfortable during this trimester. They may urinate frequently due to pressure on the bladder from the fetus. There may also be intestinal blockage and circulatory problems, especially in the legs, where clots may form due to pressure from the fetus on returning veins as they enter the abdominal cavity.

Polar body is smaller cell produced during the process of meiosis in oogenesis.

The initiation of ovulation—the release of an oocyte from the ovary—marks the transition from puberty into reproductive maturity for women. From then on, throughout a woman’s reproductive years, ovulation occurs approximately once every 28 days. Just prior to ovulation, a surge of luteinizing hormone triggers the resumption of meiosis in a primary oocyte. This initiates the transition from primary to secondary oocyte. However, as you can see in Figure, this cell division does not result in two identical cells. Instead, the cytoplasm is divided unequally, and one daughter cell is much larger than the other. This larger cell, the secondary oocyte, eventually leaves the ovary during ovulation. The smaller cell, called the first polar body, may or may not complete meiosis and produce second polar bodies; in either case, it eventually disintegrates. Therefore, even though oogenesis produces up to four cells, only one survives.

Oogenesis

The unequal cell division of oogenesis produces one to three polar bodies that later degrade, as well as a single haploid ovum, which is produced only if there is penetration of the secondary oocyte by a sperm cell.

Cleavage is a form of mitotic cell division in which the cell divides but the total volume remains unchanged; this process serves to produce smaller and smaller cells

Pre-implantation Embryonic Development

Following fertilization, the zygote and its associated membranes, together referred to as the conceptus, continue to be projected toward the uterus by peristalsis and beating cilia. During its journey to the uterus, the zygote undergoes five or six rapid mitotic cell divisions. Although each cleavage results in more cells, it does not increase the total volume of the conceptus (Figure). Each daughter cell produced by cleavage is called a blastomere (blastos = "germ," in the sense of a seed or sprout).

Approximately 3 days after fertilization, a 16-cell conceptus reaches the uterus. The cells that had been loosely grouped are now compacted and look more like a solid mass. The name given to this structure is the morula (morula = "little mulberry"). Once inside the uterus, the conceptus floats freely for several more days. It continues to divide, creating a ball of approximately 100 cells, and consuming nutritive endometrial secretions called uterine milk while the uterine lining thickens. The ball of now tightly bound cells starts to secrete fluid and organize themselves around a fluid-filled cavity, the blastocoel. At this developmental stage, the conceptus is referred to as a blastocyst. Within this structure, a group of cells forms into an inner cell mass, which is fated to become the embryo. The cells that form the outer shell are called trophoblasts (trophe = "to feed" or "to nourish"). These cells will develop into the chorionic sac and the fetal portion of the placenta (the organ of nutrient, waste, and gas exchange between mother and the developing offspring).

The inner mass of embryonic cells is totipotent during this stage, meaning that each cell has the potential to differentiate into any cell type in the human body. Totipotency lasts for only a few days before the cells' fates are set as being the precursors to a specific lineage of cells.

Pre-Embryonic Cleavages

Pre-embryonic cleavages make use of the abundant cytoplasm of the conceptus as the cells rapidly divide without changing the total volume.

As the blastocyst forms, the trophoblast excretes enzymes that begin to degrade the zona pellucida. In a process called "hatching," the conceptus breaks free of the zona pellucida in preparation for implantation.

The Primitive streak is an indentation along the dorsal surface of the epiblast through which cells migrate to form the endoderm and mesoderm during gastrulation.

Embryogenesis

As the third week of development begins, the two-layered disc of cells becomes a three-layered disc through the process of gastrulation, during which the cells transition from totipotency to multipotency. The embryo, which takes the shape of an oval-shaped disc, forms an indentation called the primitive streak along the dorsal surface of the epiblast. A node at the caudal or “tail” end of the primitive streak emits growth factors that direct cells to multiply and migrate. Cells migrate toward and through the primitive streak and then move laterally to create two new layers of cells. The first layer is the endoderm, a sheet of cells that displaces the hypoblast and lies adjacent to the yolk sac. The second layer of cells fills in as the middle layer, or mesoderm. The cells of the epiblast that remain (not having migrated through the primitive streak) become the ectoderm.

Germ Layers

Formation of the three primary germ layers occurs during the first 2 weeks of development. The embryo at this stage is only a few millimeters in length.

Each of these germ layers will develop into specific structures in the embryo. Whereas the ectoderm and endoderm form tightly connected epithelial sheets, the mesodermal cells are less organized and exist as a loosely connected cell community. The ectoderm gives rise to cell lineages that differentiate to become the central and peripheral nervous systems, sensory organs, epidermis, hair, and nails. Mesodermal cells ultimately become the skeleton, muscles, connective tissue, heart, blood vessels, and kidneys. The endoderm goes on to form the epithelial lining of the gastrointestinal tract, liver, and pancreas, as well as the lungs

Following gastrulation of the embryo in the third week, embryonic cells of the ectoderm, mesoderm, and endoderm begin to migrate and differentiate into the cell lineages that will give rise to mature organs and organ systems in the infant.

Proliferative phase is the phase of the menstrual cycle in which the endometrium proliferates.

Proliferative Phase

Once menstrual flow ceases, the endometrium begins to proliferate again, marking the beginning of the proliferative phase of the menstrual cycle (see Figure). It occurs when the granulosa and theca cells of the tertiary follicles begin to produce increased amounts of estrogen. These rising estrogen concentrations stimulate the endometrial lining to rebuild.

Recall that the high estrogen concentrations will eventually lead to a decrease in FSH as a result of negative feedback, resulting in atresia of all but one of the developing tertiary follicles. The switch to positive feedback—which occurs with the elevated estrogen production from the dominant follicle—then stimulates the LH surge that will trigger ovulation. In a typical 28-day menstrual cycle, ovulation occurs on day 14. Ovulation marks the end of the proliferative phase as well as the end of the follicular phase.

Hormone Levels in Ovarian and Menstrual Cycles

The correlation of the hormone levels and their effects on the female reproductive system is shown in this timeline of the ovarian and menstrual cycles. The menstrual cycle begins at day one with the start of menses. Ovulation occurs around day 14 of a 28-day cycle, triggered by the LH surge.

Progesterone is a reproductive hormone in women; assists in endometrial regrowth and inhibition of FSH and LH release.

Female Hormones

The control of reproduction in females is more complex. As with the male, the anterior pituitary hormones cause the release of the hormones FSH and LH. In addition, estrogens and progesterone are released from the developing follicles. Estrogen is the reproductive hormone in females that assists in endometrial regrowth, ovulation, and calcium absorption; it is also responsible for the secondary sexual characteristics of females. These include breast development, flaring of the hips, and a shorter period necessary for bone maturation. Progesterone assists in endometrial re-growth and inhibition of FSH and LH release.

In females, FSH stimulates development of egg cells, called ova, which develop in structures called follicles. Follicle cells produce the hormone inhibin, which inhibits FSH production. LH also plays a role in the development of ova, induction of ovulation, and stimulation of estradiol and progesterone production by the ovaries. Estradiol and progesterone are steroid hormones that prepare the body for pregnancy. Estradiol produces secondary sex characteristics in females, while both estradiol and progesterone regulate the menstrual cycle.

Following ovulation, the ovarian cycle enters its luteal phase, illustrated in Figure 43.15 and the menstrual cycle enters its secretory phase, both of which run from about day 15 to 28. The luteal and secretory phases refer to changes in the ruptured follicle. The cells in the follicle undergo physical changes and produce a structure called a corpus luteum. The corpus luteum produces estrogen and progesterone. The progesterone facilitates the regrowth of the uterine lining and inhibits the release of further FSH and LH. The uterus is being prepared to accept a fertilized egg, should it occur during this cycle. The inhibition of FSH and LH prevents any further eggs and follicles from developing, while the progesterone is elevated. The level of estrogen produced by the corpus luteum increases to a steady level for the next few days.

VISUAL CONNECTION

Figure 43.15 The ovarian and menstrual cycles of female reproduction are regulated by hormones produced by the hypothalamus, pituitary, and ovaries.

If no fertilized egg is implanted into the uterus, the corpus luteum degenerates and the levels of estrogen and progesterone decrease. The endometrium begins to degenerate as the progesterone levels drop, initiating the next menstrual cycle. The decrease in progesterone also allows the hypothalamus to send GnRH to the anterior pituitary, releasing FSH and LH and starting the cycles again. Figure 43.17 visually compares the ovarian and uterine cycles as well as the commensurate hormone levels.

VISUAL CONNECTION

Figure 43.17 Rising and falling hormone levels result in progression of the ovarian and menstrual cycles. (credit: modification of work by Mikael Häggström)

A trophoblast is the outer layer of cells in the blastocyst. (Blastocyst is the structure formed when cells in the mammalian blastula separate into an inner and outer layer.)

In mammals, the blastula forms the blastocyst in the next stage of development. Here the cells in the blastula arrange themselves in two layers: the inner cell mass, and an outer layer called the trophoblast. The inner cell mass is also known as the embryoblast and this mass of cells will go on to form the embryo. At this stage of development, illustrated in Figure the inner cell mass consists of embryonic stem cells that will differentiate into the different cell types needed by the organism. The trophoblast will contribute to the placenta and nourish the embryo.

The Yolk sac is a membrane associated with primitive circulation to the developing embryo; source of the first blood cells and germ cells and contributes to the umbilical cord structure.

The first of four extra-embryonic membranes to form during EMBRYOGENESIS. In REPTILES and BIRDS, it arises from endoderm and mesoderm to incorporate the EGG YOLK into the DIGESTIVE TRACT for nourishing the embryo. In placental MAMMALS, its nutritional function is vestigial; however, it is the source of INTESTINAL MUCOSA; BLOOD CELLS; and GERM CELLS. It is sometimes called the vitelline sac, which should not be confused with the VITELLINE MEMBRANE of the egg.

Zona pellucida is the protective layer around the mammalian egg. It is a thick, gel-like glycoprotein membrane that coats the oocyte and must be penetrated by sperm before fertilization can occur.

Early Embryonic Development

Fertilization is the process in which gametes (an egg and sperm) fuse to form a zygote. To ensure that the offspring has only one complete diploid set of chromosomes, only one sperm must fuse with one egg. In mammals, a layer called the zona pellucida protects the egg. At the tip of the head of a sperm cell is a structure like a lysosome called the acrosome, which contains enzymes. When a sperm binds to the zona pellucida, a series of events, called the acrosomal reactions, take place. These reactions, involving enzymes from the acrosome, allow the sperm plasma membrane to fuse with the egg plasma membrane and permit the sperm nucleus to transfer into the ovum. The nuclear membranes of the egg and sperm break down and the two haploid nuclei fuse to form a diploid nucleus or genome.

To ensure that no more than one sperm fertilizes the egg, once the acrosomal reactions take place at one location of the egg membrane, the egg releases proteins in other locations to prevent other sperm from fusing with the egg.

The development of multi-cellular organisms begins from this single-celled zygote, which undergoes rapid cell division, called cleavage (a), to form a hollow ball of cells called a blastula (b).

In mammals, the blastula forms the blastocyst in the next stage of development. Here the cells in the blastula arrange themselves in two layers: the inner cell mass, and an outer layer called the trophoblast. The inner cell mass will go on to form the embryo. The trophoblast secretes enzymes that allow implantation of the blastocyst into the endometrium of the uterus. The trophoblast will contribute to the placenta and nourish the embryo.