The ovaries are the female gonads. Paired ovals, they are each about 2 to 3 cm in length, about the size of an almond. The ovaries are located within the pelvic cavity, and are supported by the mesovarium, an extension of the peritoneum that connects the ovaries to the broad ligament. Extending from the mesovarium itself is the suspensory ligament that contains the ovarian blood and lymph vessels. Finally, the ovary itself is attached to the uterus via the ovarian ligament.

The ovary comprises an outer covering of cuboidal epithelium called the ovarian surface epithelium that is superficial to a dense connective tissue covering called the tunica albuginea. Beneath the tunica albuginea is the cortex, or outer portion, of the organ. The cortex is composed of a tissue framework called the ovarian stroma that forms the bulk of the adult ovary. Oocytes develop within the outer layer of this stroma, each surrounded by supporting cells. This grouping of an oocyte and its supporting cells is called a follicle. The growth and development of ovarian follicles will be described shortly. Beneath the cortex lies the inner ovarian medulla, the site of blood vessels, lymph vessels, and the nerves of the ovary. You will learn more about the overall anatomy of the female reproductive system at the end of this section.

The primary female reproductive organs, or gonads, are the two ovaries. Each ovary is a solid, ovoid structure about the size and shape of an almond, about 3.5 cm in length, 2 cm wide, and 1 cm thick. The ovaries are located in shallow depressions, called ovarian fossae, one on each side of the uterus, in the lateral walls of the pelvic cavity. They are held loosely in place by peritoneal ligaments.

The ovaries are covered on the outside by a layer of simple cuboidal epithelium called germinal (ovarian) epithelium. This is actually the visceral peritoneum that envelops the ovaries. Underneath this layer is a dense connective tissue capsule, the tunica albuginea. The substance of the ovaries is distinctly divided into an outer cortex and an inner medulla. The cortex appears more dense and granular due to the presence of numerous ovarian follicles in various stages of development. Each of the follicles contains an oocyte, a female germ cell. The medulla is a loose connective tissue with abundant blood vessels, lymphatic vessels, and nerve fibers.

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.

Folliculogenesis

Again, 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.

Hormonal Control of the Ovarian Cycle

The process of development that we have just described, from primordial follicle to early tertiary follicle, takes approximately two months in humans. The final stages of development of a small cohort of tertiary follicles, ending with ovulation of a secondary oocyte, occur over a course of approximately 28 days. These changes are regulated by many of the same hormones that regulate the male reproductive system, including GnRH, LH, and FSH.

As in men, the hypothalamus produces GnRH, a hormone that signals the anterior pituitary gland to produce the gonadotropins FSH and LH (Figure). These gonadotropins leave the pituitary and travel through the bloodstream to the ovaries, where they bind to receptors on the granulosa and theca cells of the follicles. FSH stimulates the follicles to grow (hence its name of follicle-stimulating hormone), and the five or six tertiary follicles expand in diameter. The release of LH also stimulates the granulosa and theca cells of the follicles to produce the sex steroid hormone estradiol, a type of estrogen. This phase of the ovarian cycle, when the tertiary follicles are growing and secreting estrogen, is known as the follicular phase.

The more granulosa and theca cells a follicle has (that is, the larger and more developed it is), the more estrogen it will produce in response to LH stimulation. As a result of these large follicles producing large amounts of estrogen, systemic plasma estrogen concentrations increase. Following a classic negative feedback loop, the high concentrations of estrogen will stimulate the hypothalamus and pituitary to reduce the production of GnRH, LH, and FSH. Because the large tertiary follicles require FSH to grow and survive at this point, this decline in FSH caused by negative feedback leads most of them to die (atresia). Typically only one follicle, now called the dominant follicle, will survive this reduction in FSH, and this follicle will be the one that releases an oocyte. Scientists have studied many factors that lead to a particular follicle becoming dominant: size, the number of granulosa cells, and the number of FSH receptors on those granulosa cells all contribute to a follicle becoming the one surviving dominant follicle.

When only the one dominant follicle remains in the ovary, it again begins to secrete estrogen. It produces more estrogen than all of the developing follicles did together before the negative feedback occurred. It produces so much estrogen that the normal negative feedback doesn’t occur. Instead, these extremely high concentrations of systemic plasma estrogen trigger a regulatory switch in the anterior pituitary that responds by secreting large amounts of LH and FSH into the bloodstream (see Figure). The positive feedback loop by which more estrogen triggers release of more LH and FSH only occurs at this point in the cycle.

It is this large burst of LH (called the LH surge) that leads to ovulation of the dominant follicle. The LH surge induces many changes in the dominant follicle, including stimulating the resumption of meiosis of the primary oocyte to a secondary oocyte. As noted earlier, the polar body that results from unequal cell division simply degrades. The LH surge also triggers proteases (enzymes that cleave proteins) to break down structural proteins in the ovary wall on the surface of the bulging dominant follicle. This degradation of the wall, combined with pressure from the large, fluid-filled antrum, results in the expulsion of the oocyte surrounded by granulosa cells into the peritoneal cavity. This release is ovulation.

In the next section, you will follow the ovulated oocyte as it travels toward the uterus, but there is one more important event that occurs in the ovarian cycle. The surge of LH also stimulates a change in the granulosa and theca cells that remain in the follicle after the oocyte has been ovulated. This change is called luteinization (recall that the full name of LH is luteinizing hormone), and it transforms the collapsed follicle into a new endocrine structure called the corpus luteum, a term meaning “yellowish body” (see Figure). Instead of estrogen, the luteinized granulosa and theca cells of the corpus luteum begin to produce large amounts of the sex steroid hormone progesterone, a hormone that is critical for the establishment and maintenance of pregnancy. Progesterone triggers negative feedback at the hypothalamus and pituitary, which keeps GnRH, LH, and FSH secretions low, so no new dominant follicles develop at this time.

The post-ovulatory phase of progesterone secretion is known as the luteal phase of the ovarian cycle. If pregnancy does not occur within 10 to 12 days, the corpus luteum will stop secreting progesterone and degrade into the corpus albicans, a nonfunctional “whitish body” that will disintegrate in the ovary over a period of several months. During this time of reduced progesterone secretion, FSH and LH are once again stimulated, and the follicular phase begins again with a new cohort of early tertiary follicles beginning to grow and secrete estrogen.

Female sex cells, or gametes, develop in the ovaries by a form of meiosis called oogenesis. The sequence of events in oogenesis is similar to the sequence in spermatogenesis, but the timing and final result are different. Early in fetal development, primitive germ cells in the ovaries differentiate into oogonia. These divide rapidly to form thousands of cells, still called oogonia, which have a full complement of 46 (23 pairs) chromosomes. Oogonia then enter a growth phase, enlarge, and become primary oocytes. The diploid (46 chromosomes) primary oocytes replicate their DNA and begin the first meiotic division, but the process stops in prophase and the cells remain in this suspended state until puberty. Many of the primary oocytes degenerate before birth, but even with this decline, the two ovaries together contain approximately 700,000 oocytes at birth. This is the lifetime supply, and no more will develop. This is quite different than the male in which spermatogonia and primary spermatocytes continue to be produced throughout the reproductive lifetime. By puberty the number of primary oocytes has further declined to about 400,000.

Beginning at puberty, under the influence of follicle-stimulating hormone, several primary oocytes start to grow again each month. One of the primary oocytes seems to outgrow the others and it resumes meiosis I. The other cells degenerate. The large cell undergoes an unequal division so that nearly all the cytoplasm, organelles, and half the chromosomes go to one cell, which becomes a secondary oocyte. The remaining half of the chromosomes go to a smaller cell called the first polar body. The secondary oocyte begins the second meiotic division, but the process stops in metaphase. At this point ovulation occurs. If fertilization occurs, meiosis II continues. Again this is an unequal division with all of the cytoplasm going to the ovum, which has 23 single-stranded chromosome. The smaller cell from this division is a second polar body. The first polar body also usually divides in meiosis I to produce two even smaller polar bodies. If fertilization does not occur, the second meiotic division is never completed and the secondary oocyte degenerates. Here again there are obvious differences between the male and female. In spermatogenesis, four functional sperm develop from each primary spermatocyte. In oogenesis, only one functional fertilizable cell develops from a primary oocyte. The other three cells are polar bodies and they degenerate.

An ovarian follicle consists of a developing oocyte surrounded by one or more layers of cells called follicular cells. At the same time that the oocyte is progressing through meiosis, corresponding changes are taking place in the follicular cells. Primordial follicles, which consist of a primary oocyte surrounded by a single layer of flattened cells, develop in the fetus and are the stage that is present in the ovaries at birth and throughout childhood.

Beginning at puberty, follicle-stimulating hormone stimulates changes in the primordial follicles. The follicular cells become cuboidal, the primary oocyte enlarges, and it is now a primary follicle. The follicles continue to grow under the influence of follicle-stimulating hormone, and the follicular cells proliferate to form several layers of granulose cells around the primary oocyte. Most of these primary follicles degenerate along with the primary oocytes within them, but usually one continues to develop each month. The granulosa cells start secreting estrogen and a cavity, or antrum, forms within the follicle. When the antrum starts to develop, the follicle becomes a secondary follicle. The granulose cells also secrete a glycoprotein substance that forms a clear membrane, the zona pellucida, around the oocyte. After about 10 days of growth the follicle is a mature vesicular (graafian) follicle, which forms a "blister" on the surface of the ovary and contains a secondary oocyte ready for ovulation.

Ovulation, prompted by luteinizing hormone from the anterior pituitary, occurs when the mature follicle at the surface of the ovary ruptures and releases the secondary oocyte into the peritoneal cavity. The ovulated secondary oocyte, ready for fertilization is still surrounded by the zona pellucida and a few layers of cells called the corona radiata. If it is not fertilized, the secondary oocyte degenerates in a couple of days. If a sperm passes through the corona radiata and zona pellucida and enters the cytoplasm of the secondary oocyte, the second meiotic division resumes to form a polar body and a mature ovum

After ovulation and in response to luteinizing hormone, the portion of the follicle that remains in the ovary enlarges and is transformed into a corpus luteum. The corpus luteum is a glandular structure that secretes progesterone and some estrogen. Its fate depends on whether fertilization occurs. If fertilization does not take place, the corpus luteum remains functional for about 10 days; then it begins to degenerate into a corpus albicans, which is primarily scar tissue, and its hormone output ceases. If fertilization occurs, the corpus luteum persists and continues its hormone functions until the placenta develops sufficiently to secrete the necessary hormones. Again, the corpus luteum ultimately degenerates into corpus albicans, but it remains functional for a longer period of time.

The female sexual response includes arousal and orgasm, but there is no ejaculation. A woman may become pregnant without having an orgasm.

Follicle-stimulating hormone, luteinizing hormone, estrogen, and progesterone have major roles in regulating the functions of the female reproductive system.

At puberty, when the ovaries and uterus are mature enough to respond to hormonal stimulation, certain stimuli cause the hypothalamus to start secreting gonadotropin-releasing hormone. This hormone enters the blood and goes to the anterior pituitary gland where it stimulates the secretion of follicle-stimulating hormone and luteinizing hormone. These hormones, in turn, affect the ovaries and uterus and the monthly cycles begin. A woman's reproductive cycles last from menarche to menopause.

The monthly ovarian cycle begins with the follicle development during the follicular phase, continues with ovulation during the ovulatory phase, and concludes with the development and regression of the corpus luteum during the luteal phase.

The uterine cycle takes place simultaneously with the ovarian cycle. The uterine cycle begins with menstruation during the menstrual phase, continues with repair of the endometrium during the proliferative phase, and ends with the growth of glands and blood vessels during the secretory phase.

Menopause occurs when a woman's reproductive cycles stop. This period is marked by decreased levels of ovarian hormones and increased levels of pituitary follicle-stimulating hormone and luteinizing hormone. The changing hormone levels are responsible for the symptoms associated with menopause.