title: Hypoxia induces miR-210, leading to anti-apoptosis in ovarian follicular cells of marine medaka Oryzias melastigma.
abstract: 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.
authors.affiliation: School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China; State Key Laboratory in Marine Pollution, Hong Kong SAR, China.
authors.forename: Anna Chung-Kwan
authors.initials: AC
authors.lastname: Tse
authors.affiliation: School of Life Sciences, Hong Kong Bioinformatics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Jing-Woei
authors.initials: JW
authors.lastname: Li
authors.affiliation: School of Life Sciences, Hong Kong Bioinformatics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Ting-Fung
authors.initials: TF
authors.lastname: Chan
authors.affiliation: School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China; State Key Laboratory in Marine Pollution, Hong Kong SAR, China.
authors.forename: Rudolf Shiu-Sun
authors.initials: RS
authors.lastname: Wu
authors.affiliation: School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China; State Key Laboratory in Marine Pollution, Hong Kong SAR, China. Electronic address: balllai@hku.hk.
authors.forename: Keng-Po
authors.initials: KP
authors.lastname: Lai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009990:Oryzias / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006080:Ovarian Follicle / Q000201:enzymology / Q000503:physiopathology*; D013312:Stress, Physiological / Q000235:genetics
chemical_list: D035683:MicroRNAs
keywords: Apoptosis; Hypoxia; Marine medaka; Mirna; Ovarian follicular cells