Hypoxia is a major global problem that impairs reproductive functions and reduces the quality and quantity of gametes and the fertilization success of marine fish. Nevertheless, the detailed molecular mechanism underlying
hypoxia-induced female reproductive impairment remains largely unknown. There is increasing evidence that
miRNA is vital in regulating ovarian functions and is closely associated with female fertility in humans. Certain
miRNAs that regulate apoptotic genes can be induced by
hypoxia, resulting in cell apoptosis. Using primary ovarian follicular cells of the marine medaka, Oryzias melastigma, as a model, we investigated the response of miR-210 to hypoxic stress in ovarian tissues to see if it would interrupt reproductive functions. A significant induction of miR-210 was found in primary ovarian follicular cells exposed to
hypoxia, and gene ontology analysis further highlighted the potential roles of miR-210 in cell proliferation, cell differentiation, and cell apoptosis. A number of miR-210 target apoptotic genes, including Deleted in
liver cancer 1
protein (DLC1), STE20-like
serine/threonine-protein kinase (SLK),
tumor necrosis factor receptor superfamily member 10b (TNFRSF10B), RNA binding motif
protein 25 (RBM25), and
Ubiquitin-specific-processing protease 7 (USP7), were identified. We further showed that ectopic expression of miR-210 would result in down-regulation of these apoptotic genes. On the other hand, the inhibition of miR-210 promoted apoptotic cell death and the expression of apoptotic marker -
caspase 3 in follicular cells under hypoxic treatment, supporting the regulatory role of miR-210 in ovarian cell apoptosis. This study provides new insights on how
hypoxia induces miR-210, leading to anti-apoptosis in ovarian follicular cells in fish, which is fundamentally important in environmental sciences and reproductive biology.