MicroRNA-21 is involved in oocyte maturation, blastocyst formation, and pre-implantation embryo development

Abstract

Follicular fluid is one source of microRNAs (miRNAs). These miRNAs originate from oocytes and their neighboring cells. The changes in the miRNAs profile in the follicular fluid could alter folliculogenesis and oocyte maturation, and lead to infertility. Polycystic ovary syndrome (PCOS) patients have increased miR-21 levels in their sera, granulosa cells, and follicular fluid, and this mi-RNA plays a role in the pathophysiology and follicular dysfunction of PCOS patients. In the current study, we intend to examine whether expression levels of miR-21 influence oocyte maturation and embryo development. We examined miR-21 over-expression and down-regulation of miR-21 by miR-off 21 during in vitro maturation (IVM) to assess its influence on oocyte maturation and embryo development in mice. Over-expression of miR-21 in cumulus cells decreased expansion, meiotic progression, Glutathione-S-transferase GSH levels, and decreased expressions of Bmpr2 and Ptx3 genes. Subsequently, we noted that in vitro fertilization, and the cleavage rate and blastocyst formation significantly increased in cumulus oocyte complexes (COCs) that over-expressed miR-21. Inhibition of miR-21 by miR-off 21 led to increased cumulus expansion and GSH levels, along with decreased cleavage rate and blastocyst formation by alterations in Cdk2ap1 and Oct4 gene expressions. However, oocyte progression from the germinal vesicle (GV) to the metaphase II (MII) stage was not significant. miR-21 altered the gene expression levels in cumulus cells and influenced cytoplasmic oocyte maturation, cumulus expansion, and subsequent embryonic development in mice.