Hypoxia induces miR-210, leading to anti-apoptosis in ovarian follicular cells of marine medaka Oryzias melastigma

Anna Chung-Kwan TSE, Jing-Woei LI, Ting-Fung CHAN, Shiu Sun Rudolf WU, Keng-Po LAI

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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. Copyright © 2015 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)189-196
JournalAquatic Toxicology
Volume165
Early online date05 Jun 2015
DOIs
Publication statusPublished - Aug 2015

Fingerprint

Oryzias
apoptosis
hypoxia
Apoptosis
gene
protein
cells
MicroRNAs
Fishes
genes
gamete
reproductive biology
fish
TNF-Related Apoptosis-Inducing Ligand Receptors
Genes
tumor
environmental science
Gene Ontology
RNA
fertility

Citation

Tse, A. C.-K., Li, J.-W., Chan, T.-F., Wu, R. S.-S., & Lai, K.-P. (2015). Hypoxia induces miR-210, leading to anti-apoptosis in ovarian follicular cells of marine medaka Oryzias melastigma. Aquatic Toxicology, 165, 189-196. doi: 10.1016/j.aquatox.2015.06.002

Keywords

  • Hypoxia
  • Apoptosis
  • Marine medaka
  • Mirna
  • Ovarian follicular cells