Presence of Fas-Fas ligand system and bcl-2 gene products in cells and fluids from gonadotropin-stimulated human ovaries

Apoptosis, or programmed cell death, is an important mechanism for the regu lation of embryonic development and tissue homeostasis. It is coordinated b y a number of molecules including the Fas-Fas ligand (FasL) system and bcl- 2. The purpose of this study was to characterize the expression of these mo lecules in human oocytes and cumulus cells from gonadotropin-stimulated hum an ovaries and to determine whether the presence of soluble Fas (sFas), sol uble FasL, or interferon-gamma in follicular fluid (FF) correlated with apo ptosis in cumulus cells, oocyte maturation, and embryo quality. Levels of s Fas were significantly higher in FF containing immature oocytes compared wi th those containing atretic oocytes (P < 0.05; FF containing mature oocytes had highly variable levels of sFas. Levels of sFas in FF did not correlate with either fertilization, embryo quality resulting from fertilized oocyte s, or apoptosis rate in cumulus cells. Fas was expressed in both unfertiliz ed oocytes and cumulus cells, whereas FasL expression was not usually detec ted in these cell types. Messenger RNA for bcl-2 was delectable in both fre shly isolated oocytes and cumulus cells but was mot demonstrable following 24 h of culture that coincided with a significant increase of apoptosis in cumulus cells. Our results indicate that soluble forms of the Fas-FasL syst em are present in FF from gonadotropin-stimulated human ovaries and suggest that this system may play a role in preventing oocyte atresia during folli culogenesis but is probably not important for apoptotic events in cumulus c ells and oocytes after fertilizaton failure. Apoptosis in this case may be facilitated by the downregulation of bcl-2. Further studies on the expressi on of these molecules in follicles containing atretic oocytes and immature oocytes are needed to confirm this new hypothesis.