Apparently balanced reciprocal translocations are one of the most common genetic causes of male infertility. The commonly accepted underlying pathophysiological mechanism is that they impair meiosis but few studies have been conducted and not for each reported translocation. Here, we sought to investigate the hypothesis of an altered expression of spermatogenesis genes located at the breakpoints, at least in some cases, as already described in other constitutional and somatic diseases.

We included 13 unrelated infertile men carrying apparently balanced reciprocal translocations that were identified by karyotyping. We performed optical genome mapping (OGM) according to the Bionano protocol and using the Saphyr® instrument and Bionano Solve® and Access® software for data analysis. Gene content at the breakpoints and flanking regions was investigated. Twelve out of 13 translocations could be characterized by OGM. The undetected translocation had breakpoints in the heterochromatic regions of both chromosome Y and 16 long arms. Preliminary analysis of gene content at the breakpoints revealed the disruption of at least one gene involved in spermatogenesis or sperm function and a possible positional effect for another patient.

In conclusion, this study underlines the added-value of using OGM to characterize apparently balanced structural variations in infertility. These analyses could allow to identify new genes involved in reproductive disorders and refine genotype-phenotype correlations.