Purpose of review: To highlight the significance of the abnormal DNA repair mechanism in male infertility.
Recent findings: DNA repair defects cause a variety of spermatogenic defects in mouse models. Evidence is accumulating to demonstrate the importance of DNA repair defects in human nonobstructive azoospermia. Epigenetic changes may also play a crucial role in infertility.
Summary: The DNA in the cell needs to be constantly repaired to ensure fidelity of DNA replication, to maintain genome stability and to ensure propagation of species. The DNA repair and recombination machineries are highly conserved across the species and inactivation of these pathways may lead to replication and recombination errors. This review summarizes the different types of DNA lesions and DNA repair pathways, particularly focusing on highly conserved meiotic regulators, the DNA mismatch repair proteins. Targeted deletions of some of these proteins result in infertility and predisposes to tumor in mutant mouse models. There is evidence for loss of some of these proteins in human male infertility. Because defective DNA repair is associated with a mutator phenotype, the risk of transmission to the offspring of these otherwise infertile men conceived using an assisted reproductive technology needs further evaluation.