Pre-ovulatory intercellular regulation of miR-125a-3p within mouse ovarian follicles

Abstract

miR-125a-3p, a post-transcription regulator of Fyn kinase, is expressed in mouse pre-ovulatory follicles; its expression within the follicle decreases toward ovulation. Our aim was to follow the synthesis of miR-125a-3p and regulation of its expression in all follicular compartments, focusing on intercellular communication. Mural granulosa cells (GCs) or cumulus cells (CCs) were transfected with either scrambled-miR (negative control) or miR-125a-3p mimic. Freshly isolated GCs or CCs were incubated overnight in culture media conditioned by transfected cells. To examine a possible role of gap junctions in the regulation of miR-125a-3p, we incubated large antral follicles in the presence of carbenoxolone, a gap-junction inhibitor, and triggered them to mature with hGC. Levels of miR-125a family members in GCs, CCs, oocytes, and culture media were measured by qPCR. We showed that miR-125a-3p is synthesized by all follicular components, but is regulated within the follicle as a whole. It is secreted by mural-GCs and taken up by CCs, where it remains functional, and vice versa, mural-GCs can take up miR-125a-3p secreted by CCs. miR-125a-3p is transcribed and accumulated in oocytes throughout oogenesis. Transcriptionally quiescent GV oocytes utilize their accompanying follicular cells to monitor the level of miR-125a-3p within them, as indicated in an ex vivo follicle culture. Our study reveals that miR-125a-3p expression is modulated by a network of intercellular communications within pre-ovulatory follicles, thus enabling a coordinated decrease of miR-125a-3p toward ovulation.

The Involvement of the microRNAs miR-466c and miR-340 in the Palmitate-Mediated Dysregulation of Gonadotropin-Releasing Hormone Gene Expression

“…miR-503, for instance, is a potent ovarian microRNA with crucial functions in follicle formation, maturation, and the luteinization process [44][45][46]. Similar reproductive connections are noted for miR-181b, with its strong involvement in the sexual reproduction of boars [47][48][49], and miR-125a with differential expression levels from oogenesis to ovulation in mice [50], indicating their potential roles in fatty acid-induced reproductive dysfunction outside the scope of our experimental paradigm.…”

Small-extracellular vesicles and their microRNA cargo from porcine follicular fluids: the potential association with oocyte quality

“…Both are members of the mir-10 family and were detected in human FF microvesicles [ 56 ]. A recent study demonstrated that miR-125a can be transcribed by all follicular components and play a role in intercellular communication within the follicle [ 59 ]. In mice, miR-125a and miR-125b were highly expressed in GV compared to MII oocytes, and it was also found that they play an important role in regulating maternal genes and zygotic genome activation [ 60 ].…”