title: MicroRNA-378 regulates oocyte maturation via the suppression of aromatase in porcine cumulus cells.
abstract: We sought to investigate whether miR-378 plays a role in cumulus cells and whether the manipulation of miRNA levels in cumulus cells influences oocyte maturation in vitro. Cumulus-oocyte complexes (COCs) from ovarian follicles had significantly lower levels of precursor and mature miR-378 in cumulus cells surrounding metaphase II (MII) oocytes than cumulus cells surrounding germinal vesicle (GV) oocytes, suggesting a possible role of miR-378 during COC maturation. Overexpression of miR-378 in cumulus cells impaired expansion and decreased expression of genes associated with expansion (HAS2, PTGS2) and oocyte maturation (CX43, ADAMTS1, PGR). Cumulus cell expression of miR-378 also suppressed oocyte progression from the GV to MII stage (from 54 ± 2.7 to 31 ± 5.1%), accompanied by a decrease of growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15), zona pellucida 3 (ZP3), and CX37 in the oocytes. Subsequent in vitro fertilization resulted in fewer oocytes from COCs overexpressing miR-378 reaching the blastocyst stage (7.3 ± 0.7 vs. 16.6 ± 0.5%). miR-378 knockdown led to increased cumulus expansion and oocyte progression to MII, confirming a specific effect of miR-378 in suppressing COC maturation. Aromatase (CYP19A1) expression in cumulus cells was also inhibited by miR-378, leading to a significant decrease in estradiol production. The addition of estradiol to IVM culture medium reversed the effect of miR-378 on cumulus expansion and oocyte meiotic progression, suggesting that decreased estradiol production via suppression of aromatase may be one of the mechanisms by which miR-378 regulates the maturation of COCs. Our data suggest that miR-378 alters gene expression and function in cumulus cells and influences oocyte maturation, possibly via oocyte-cumulus interaction and paracrine regulation.
authors: Department of Animal and Poultry Science, University of Guelph, Guelph, Ontario, Canada; and.
authors: Bo
authors: B
authors: Pan
authors: Department of Animal and Poultry Science, University of Guelph, Guelph, Ontario, Canada; and.
authors: Derek
authors: D
authors: Toms
authors: Laboratory of Germ Cell Biology, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, China.
authors: Wei
authors: W
authors: Shen
authors: Department of Animal and Poultry Science, University of Guelph, Guelph, Ontario, Canada; and jli@uoguelph.ca.
authors: Julang
authors: J
authors: Li
mesh_terms: D000818:Animals; D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D054885:Cumulus Cells / Q000378:metabolism* / Q000502:physiology; D015536:Down-Regulation / Q000235:genetics; D004958:Estradiol / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D059471:In Vitro Oocyte Maturation Techniques; D035683:MicroRNAs / Q000502:physiology*; D009865:Oocytes / Q000502:physiology*; D009866:Oogenesis / Q000235:genetics*; D019899:Paracrine Communication / Q000235:genetics; D013552:Swine
chemical_list: D035683:MicroRNAs; D004958:Estradiol; D001141:Aromatase
keywords: cumulus; microRNA-378; oocyte
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