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Eif4enif1 haploinsufficiency disrupts oocyte mitochondrial dynamics and leads to subfertility

ABSTRACT: Premature ovarian insufficiency (POI) refers to the loss of ovarian function before the age of 40, which is among the various contributing factors towards infertility issues. Several studies have previously reported dominantly inherited POI symptoms in families carrying likely contributing heterozygous EIF4ENIF1 mutations. However, this impact of EIF4ENIF1 haploinsufficiency was barely studied in animal models to reveal the underlying molecular changes that relate to infertility. In this study, we demonstrated that haploinsufficiency of Eif4enif1 caused mouse subfertility, impaired oocyte maturation and partial early embryo developmental arrest. By dual-omic sequencing, we revealed that Eif4enif1-deficiency led to significantly altered transcriptome and translatome in mouse oocytes, which led to the further discovery of abnormal mitochondrial hyperfusion with altered mitochondria-associated ribonucleoprotein domain (MARDO) distribution in Eif4enif1-dificient oocytes. This study provided new insight into the molecular mechanism underlying clinical fertility failures, and added new evidences to discovering new therapeutic targets towards infertility.

ORGANISM(S): Mus musculus

PROVIDER: GSE234050 | GEO | 2023/11/27

REPOSITORIES: GEO

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