Novel variants in MEI1 cause female infertility characterized by early embryonic arrest and implantation failure

Early embryonic arrest (EEA) and implantation failure are prevalent causes of female infertility, with genetic factors playing a significant role. MEI1 is a crucial gene for meiotic chromosome synapsis and is essential for the formation of double-strand breaks (DSBs) during germ cell meiosis. MEI1 variants contribute to EEA and implantation failure. In this study, we reported newly identified mutations in MEI1 that broaden the genetic spectrum associated with embryonic abnormalities.

Female patients with primary infertility characterized by EEA and implantation failure were recruited, and peripheral blood samples were collected. Whole-exome sequencing was performed, and the identified variants were confirmed by Sanger sequencing. Bioinformatics tools were used to predict the pathogenicity of these variants. Wild-type and mutant plasmids were constructed in vitro and transfected into HEK293T cells. The effects of the variants on the expression and function of MEI1 were investigated via real-time quantitative PCR, western blotting, and immunofluorescence assays.

We identified a novel homozygous variant and a compound heterozygous variant in MEI1 from two unrelated families. Analysis using multiple bioinformatics tools revealed that these variants are rare and may be deleterious. In vitro experiments revealed that these mutations do not alter the subcellular localization of MEI1 but significantly affect its mRNA and protein expression levels, potentially leading to impaired protein function.

These biallelic variants in MEI1 were associated with EEA and implantation failure. Our findings expand the known mutation spectrum of MEI1 and provide further evidence supporting the causal relationship between MEI1 variants and female infertility.