Globozoospermia is a condition that affects only males. It is characterized by abnormal sperm and leads to an inability to father biological children (infertility).

Normal sperm cells have an oval-shaped head with a cap-like covering called the acrosome. The acrosome contains enzymes that break down the outer membrane of an egg cell, allowing the sperm to fertilize the egg. The sperm cells of males with globozoospermia, however, have a round head and no acrosome. The abnormal sperm are unable to fertilize an egg cell, leading to infertility.

Globozoospermia is most commonly caused by mutations in the DPY19L2 gene, which are found in about 70 percent of men with this condition. Mutations in other genes likely also cause globozoospermia.

The DPY19L2 gene provides instructions for making a protein that is found in developing sperm cells. The DPY19L2 protein is involved in the development of the acrosome and elongation of the sperm head, which are integral steps in sperm cell maturation. Mutations in the DPY19L2 gene result in a loss of functional DPY19L2 protein. As a result, sperm cells have no acrosome and do not elongate properly. Without an acrosome, the abnormal sperm are unable to get through the outer membrane of an egg cell to fertilize it, leading to infertility in affected men. Researchers have described other characteristics of the abnormal sperm cells that make fertilization of an egg cell difficult, although it is not clear how changes in the DPY19L2 gene are involved in development of these characteristics.

Normal Function

The DPY19L2 gene provides instructions for making a protein that is found in developing sperm cells. The DPY19L2 protein plays a role in the development of the acrosome, a cap-like structure in the head of sperm cells. The acrosome contains enzymes that break down the outer membrane of egg cells, allowing the sperm to fertilize an egg.

The developing acrosome is attached to the nucleus of the cell. The DPY19L2 protein, which is found within the membrane of the nucleus, helps attach the forming acrosome to the nuclear membrane. As the acrosome develops and the sperm cell matures, the acrosome moves to the tip of the head of the sperm, which helps the head elongate into an oval shape.

Health Conditions Related to Genetic Changes

Globozoospermia

At least 17 DPY19L2 gene mutations have been found in men with globozoospermia, a condition characterized by abnormal sperm cells that have a round head and no acrosome. Approximately 70 percent of men with this condition have mutations in DPY19L2. Most of these mutations delete large regions of the gene or the whole gene. Others change single protein building blocks (amino acids) in the DPY19L2 protein. These mutations lead to a loss of functional DPY19L2 protein. Without this protein, the forming acrosome is not attached to the nucleus and is removed from the cell. As a result, sperm cells have no acrosome and the head of the sperm does not elongate. The abnormal sperm are unable to get through the outer membrane of an egg cell to fertilize it, leading to an inability to father biological children (infertility) in affected men. Researchers have described other characteristics of the abnormal sperm cells that make fertilization of an egg cell difficult, although it is not clear how changes in the DPY19L2 gene are involved in development of these characteristics.

Other Names for This Gene

• D19L2_HUMAN
• dpy-19 like 2 (C. elegans)
• dpy-19-like 2 (C. elegans)
• FLJ32949
• probable C-mannosyltransferase DPY19L2
• protein dpy-19 homolog 2
• SPATA34
• spermatogenesis associated 34
• SPGF9

Genomic Location

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Globozoospermia is a rare condition that is estimated to affect 1 in 65,000 men. It is most common in North Africa, where it accounts for approximately 1 in 100 cases of male infertility.