Mutations in genes coding for synaptonemal complex proteins and their impact on human fertility

Abstract

Human infertility is often classified as idiopathic in both males and females. Meiotic errors may account for at least part of these cases. As the synaptonemal complex (SC, a mei-osis-specific protein scaffold) is essential for successful meio-sis progression, in this paper, we analyzed the mutations in genes coding for SC components described in infertile pa-tients to assess to what extent alterations in the SC can be related to human infertility. So far, mutations in SYCP3 and SYCE1 genes have been reported. While most SYCP3 muta-tions are heterozygous mutations with dominant-negative effect on the region encoding the C-terminal coiled coil of the protein, SYCE1 mutations are homozygous, which is con-sistent with a recessive inheritance. Similarities and differ-ences between males and females as well as between mice and humans have been found and are discussed herein. The results suggest that a low percentage of human infertility cases may be explained by mutations in genes coding for SC components. The characterization of these mutations, to-gether with available information from the study of knock-out mice, will enable a deeper understanding of the underly-ing molecular bases for some of the cases of idiopathic infer-tility.