MicroRNA-224 is involved in the regulation of mouse cumulus expansion by targeting Ptx3

作者:Yao Guidong; Liang Meng; Liang Ning; Yin Mianmian; Lu Mingrong; Lian Jie; Wang Yong; Sun Fei*
来源:Molecular and Cellular Endocrinology, 2014, 382(1): 244-253.
DOI:10.1016/j.mce.2013.10.014

摘要

MicroRNAs (miRNAs) are indicated to regulate ovarian development in a cell- or stage-specific manner. Our previous study showed that miR-224 is involved in TGF-beta 1-mediated follicular granulosa cell (GC) growth and estradiol (E2) production during the transition from the preantral to early antral stage by targeting Smad4. In this study, miR-224 was found to target pentraxin 3 (Ptx3), a gene critical for cumulus expansion during ovulation. In addition, PTX3 was up-regulated in mouse mural GCs and cumulus-oocyte complexes (COCs) by TGF-beta 1 treatment, which was partially mediated by miR-224. The effect of miR-224 during ovulation was further examined in vitro and in vivo by construction of an adenovirus-mediated expression vector for miR-224 (Ad-miR-224). In vitro studies demonstrated that miR-224 could perturb cumulus expansion in EGF-stimulated COCs by decreasing PTX3 secretion. In vivo studies also showed that injection of Ad-miR-224 into ovarian bursa decreased PTX3 expression and disrupted ovulation, which led to a decreased number of implantation sites and offspring being born. These results indicate that miR-224 may affect ovulation and subsequent embryo development by targeting Ptx3, suggesting potential roles for miRNAs in offering new treatments for ovulation disorder-associated infertility, or, conversely, designing new contraceptives.