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

In affected males, almost all sperm cells have abnormally large and misshapen heads. The head of the sperm cell contains the male's genetic information that is to be passed on to the next generation. Normally, the head of a sperm cell contains one copy of each chromosome. In men with macrozoospermia, the sperm cell head contains extra chromosomes, usually four copies of each instead of the usual one. This additional genetic material accounts for the larger head size of the sperm cell. Additionally, instead of having one tail (flagellum) per sperm cell, affected sperm have multiple flagella, most often four.

Because of the additional genetic material, if one of these abnormal sperm cells combines with an egg cell, the embryo will not develop or the pregnancy will result in miscarriage.

Mutations in the AURKC gene cause macrozoospermia. The AURKC gene provides instructions for making a protein called aurora kinase C. This protein is abundant in male testes, which are the male reproductive organs in which sperm are produced and stored. In the testes, this protein regulates the division of sperm cells. Aurora kinase C ensures that the mechanisms for cell division are in place and helps chromosomes properly align with each other so that every new sperm cell contains one copy of each chromosome after cell division.

AURKC gene mutations that cause macrozoospermia lead to the production of a nonfunctional protein or a protein that is quickly broken down. This lack of aurora kinase C blocks cell division in sperm cells. Without cell division, the chromosomes are not split among multiple new sperm cells. As a result, affected sperm cells contain extra chromosomes, usually four copies of each instead of the usual one.

Normal Function

The AURKC gene provides instructions for making a protein called aurora kinase C. This protein regulates certain events during cell division. Cell division occurs when a cell replicates and splits its contents, separating into two new cells. Aurora kinase C helps the two dividing cells separate from each other and ensures that these cells each contain a complete set of chromosomes. Aurora kinase C is most abundant in male testes, which are the male reproductive organs in which sperm are produced and stored. In the testes, this protein regulates the division of sperm cells, ensuring that every new sperm cell divides properly and contains one copy of each chromosome.

Health Conditions Related to Genetic Changes

Macrozoospermia

At least four mutations in the AURKC gene have been found to cause macrozoospermia. This condition causes males to have abnormal sperm, which leads to an inability to father biological children (infertility). AURKC gene mutations that cause macrozoospermia lead to the production of a nonfunctional protein or a protein that is quickly broken down. One mutation that is a frequent cause of this condition in men of North African descent deletes a single DNA building block (nucleotide) from the AURKC gene (written 144delC). The protein produced from the altered gene is abnormally short and nonfunctional.

A lack of aurora kinase C blocks cell division in sperm cells. As a result, sperm cells have extra chromosomes, usually four copies of each instead of the usual one. This increase in chromosome number enlarges the sperm cell head and leads to the presence of multiple tails (flagella). Because of the additional genetic material, if one of these abnormal sperm cells combines with an egg cell, the embryo will not develop or the pregnancy will result in miscarriage.

Other Names for This Gene

• AIK3
• AIK3 protein kinase
• ARK-3
• ARK3
• AurC
• aurora-related kinase 3
• aurora/IPL1-like kinase 3
• aurora/IPL1-related kinase 3
• serine-threonine-protein kinase 13
• serine/threonine-protein kinase aurora-C
• STK13

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.

Macrozoospermia is estimated to affect 1 in 10,000 males in North Africa. The prevalence of the condition outside this region is unknown.