title: MicroRNA-224 delays oocyte maturation through targeting Ptx3 in cumulus cells.
abstract: MicroRNAs (miRNAs) have been improved to regulate oocyte development in a cell- or stage-specific manner. In this study, we aimed to clarify microRNA-224's (miR-224) role in cumulus cells (CCs), to find out whether a change level of miR-224 in CCs could influence the maturation of oocyte. We found that overexpression of miR-224 of CCs led to the impairment of cell expansion, along with a decrease in the gene expression associated with cell expansion and maturation of oocyte. The increased expression of miR-224 in CC interrupted oocyte cell cycle at the GV stage. The GDF9, BMP15 and ZP3 of the oocytes were also down-regulated. The following in vitro fertilization had yielded a lower number of oocytes from cumulus-oocyte complexes (COCs) overexpressing miR-224 when reaching the blastocyst stage. The suppressive effect of miR-224 in the maturation of COC is validated by the miR-224 knockdown model, where the expansion of cumulus cell was increased and oocyte was developed to MII stage. In addition, the expression of aromatase in CCs was down-regulated by miR-224, resulting in a decreased level of estradiol (E2). A further investigation found that miR-224 down-regulated the expression of protein and mRNA of Ptx3 by targeting its 3'UTR. Our study revealed that miR-224 regulates the gene expression and function of CCs, which influences the maturation of oocyte, at least in part, via targeting Ptx3.
authors.affiliation: Center for Reproductive Medicine, Shandong University, Jinan 250001, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan 250001, China; The Key Laboratory for Reproductive Endocrinology of Ministry of Education, Jinan 250001, China.
authors.forename: Xiufang
authors.initials: X
authors.lastname: Li
authors.affiliation: Center for Reproductive Medicine, Shandong University, Jinan 250001, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan 250001, China; The Key Laboratory for Reproductive Endocrinology of Ministry of Education, Jinan 250001, China.
authors.forename: Huidan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Center for Reproductive Medicine, Shandong University, Jinan 250001, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan 250001, China; The Key Laboratory for Reproductive Endocrinology of Ministry of Education, Jinan 250001, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: Department of Traditional Chinese Medicine, Provincial Hospital Affiliated to Shandong University, Jinan 250022, China. Electronic address: wangzhongqing81@126.com.
authors.forename: Zhongqing
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D055430:Bone Morphogenetic Protein 15 / Q000235:genetics / Q000378:metabolism; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D054885:Cumulus Cells / Q000166:cytology / Q000378:metabolism*; D004527:Egg Proteins / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D005307:Fertilization in Vitro; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D055429:Growth Differentiation Factor 9 / Q000235:genetics / Q000378:metabolism; D059471:In Vitro Oocyte Maturation Techniques / Q000662:veterinary*; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D020320:Oligoribonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D061251:Primary Cell Culture; D000683:Serum Amyloid P-Component / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013552:Swine; D000099153:Pentraxins
chemical_list: D001141:Aromatase; D055430:Bone Morphogenetic Protein 15; D002097:C-Reactive Protein; D004527:Egg Proteins; D004958:Estradiol; D006023:Glycoproteins; D055429:Growth Differentiation Factor 9; D035683:MicroRNAs; D020320:Oligoribonucleotides, Antisense; D000683:Serum Amyloid P-Component; D000099153:Pentraxins
keywords: Cumulus; Cumulus-oocyte complexes; Oocyte; Pentraxin 3; microRNA-224