Detection of candidate nectin gene mutations in infertile men with severe teratospermia

Approximately 40% of infertile men have an abnormal semen analysis, resulting from either abnormalities of sperm production (defective spermatogenesis) or sperm shape (defective spermiogenesis). This latter process is dependent upon the function of Sertoli cells, which maintain specialized junctional complexes with germ cells. Nectins, members of the immunoglobulin superfamily, participate in formation of these dynamic complexes. Male mice in which the nectin-2 or nectin-3 gene is knocked out are sterile. Their spermatozoa exhibit severe teratospermia, altered motility, and an impaired ability to fertilize eggs. We asked whether mutations in the protein coding regions of the nectin-2 (aka PVRL2) and nectin-3 (aka PVRL3) genes could be detected in men from infertile couples whose semen analysis revealed unimpaired sperm production, judged by normal sperm concentration, but severe abnormalities in sperm shape.

Ejaculates were snap frozen in liquid nitrogen and later submitted for Sanger analysis of these two genes, to detect mutations in their protein coding regions.

Eighty-nine of 455 ejaculates (19.5%) met the inclusion criteria for study. Two of the 56 samples that were successfully analyzed for nectin-2 (3.6%) and one of 73 (1.3%) analyzed for nectin-3 possessed possibly damaging mutations.

Despite the small-scale nature of the study, at least two low-frequency deleterious variants were identified. These results suggest the need for a larger-scale study of sequence variants in the nectins in severe teratospermia.