Regulation of oocyte meiotic maturation by somatic cells.

In preovulatory follicles, each oocyte is surrounded by numerous layers of cumulus cells, forming the cumulus cell-oocyte complex. An LH surge induces meiotic resumption of the oocyte to progress to metaphase II. Because the expression of LH receptors is not detected in the oocyte and is minimal (negligible) in cumulus cells as compared with granulosa cells, secondary factors from granulosa cells are required to induce the ovulation process. One of the key factors secreted from granulosa cells is an EGF-like factor that activates the EGFR-ERK1/2 pathway in cumulus cells. The activated ERK1/2 pathway is not only involved in gene expression but also essential for the close of gap-junctional communication among cumulus cells and between cumulus cells and the oocyte. Closing gap-junctional communication decreases the amount of cGMP and/or cAMP to transfer into the oocyte, which requires activation of phosphodiesterase type III (PDE3) in the oocyte. PDE3 brakes down cAMP to decrease PKA activity in the oocyte. This decrease in PKA activity induces activation of CDK1 to resume meiosis from the germinal vesicle stage. Thus, the functions of cumulus cells that are regulated by granulosa cell-secreted factors are essential for oocyte meiotic resumption and maturation with developmental competence.