Genotype-specific differences in infertile men due to loss-of-function variants in M1AP or ZZS genes

ABSTRACT: Male infertility has been linked to M1AP. In mice, M1AP interacts with the ZZS proteins SHOC1/TEX11/SPO16, promoting DNA class I crossover formation during meiosis. To determine whether M1AP and ZZS proteins are involved in human male infertility by recombination failure, we screened for biallelic/hemizygous loss-of-function (LoF) variants in the human genes to select men with presumed protein deficiency (N=24). After in-depth characterisation of testicular phenotypes, we identified gene-specific meiotic impairments: men with ZZS deficiency shared an early meiotic arrest. Men with LoF variants in M1AP exhibited a predominant metaphase I arrest with rare haploid round or even elongated spermatids. These differences were explained by different recombination failures: deficient ZZS function l

SUBMITTER: Nadja Rotte 

PROVIDER: S-SCDT-10_1038-S44321-025-00244-0 | biostudies-other |

REPOSITORIES: biostudies-other