The mammalian target of rapamycin (mTOR) signaling pathway functions as a central regulator of cell growth, proliferation, and survival. We previously reported that during meiotic maturation, the expression levels of mTOR in oocytes remain similar from the germinal vesicle (GV) stage to metaphase II (MII). To investigate the role played by mTOR during meiotic resumption, we cultured murine cumulus oocyte complexes (COCs) in the presence of mTOR inhibitors. mTOR expression was detected in the cumulus cells. The COCs were cultured for 18 h in a medium containing dbcAMP with or without the mTOR inhibitor PI-103 or rapamycin. We observed cumulus expansion but the oocytes were arrested at the GV stage. These oocytes were then transferred to fresh maturation medium containing FSH with or without an mTOR inhibitor before culturing for 8 more hours. We found premature development of the first polar body in oocytes treated with the mTOR inhibitor. This result suggests that mTOR inhibition induces early progression of oocytes. Further, when GV-stage oocytes were cultured for 18 h in maturation medium lacking FSH but containing the mTOR inhibitor PI-103 or rapamycin, the cumulus cells expanded and the first polar body successfully developed. In addition, we found that the mRNA expression of hyaluronan synthase (HAS) in the cumulus cells increased after treatment with the mTOR inhibitor. In conclusion, our data suggest a role for mTOR signaling during cumulus expansion and meiotic maturation in mice. In the presence of an mTOR inhibitor, cumulus expansion occurred and meiotic maturation progressed without gonadotropin stimulation.
02 - 04 Sep 2014
World Congress of Reproductive Biology