Maturation, Aging and Death in Reproductive Tissues
(W642) APOPTOSIS IS REGULATED BY SOLUBLE FAS DURING LUTEOLYSIS IN LUTEAL CELLS OF MOUSE OVARIES.
Manabe, Noboru1, Komatsu, Kohji 1, Kiso, Minako1, Goto, Yasufumi1, Anan, Sayuri 1, Li, Junyou1, 1 University of Tokyo, Ibaraki-Iwama, Japan
ABSTRACT- During luteolysis, luteal cell apoptosis is induced by the Fas ligand (FasL)/Fas system. In mouse luteal bodies, we demonstrated the mRNA expression of a soluble form of Fas (FasB), which binds to FasL and prevents apoptosis induction. By in situ hybridization, strong expression of FasB mRNA was observed in normal luteal bodies, in which no TUNEL-positive apoptotic cells were detected, but negative/trace expression was observed in regressing luteal bodies, in which many apoptotic cells were observed. Immunohistochemical staining demonstrated that Fas and tumor necrosis factor (TNF) alpha were localized in both normal and regressing luteal bodies, but interferon (IFN) gamma was localized only in regressing luteal bodies. Apoptosis was induced in primary cultured luteal cells, when the cells were pretreated with TNFa and IFNg, then incubated with TNFa, IFNg and mouse recombinant FasL (rFasL). However, there was no apoptosis detected in the cells when they were treated with rFasL alone, TNFa alone, IFNg alone, TNFa and rFasL, IFNg and rFasL, or TNFa and IFNg. Fas mRNA expression in cultured luteal cells was up-regulated following treatment with TNFa, IFNg or TNFa and IFNg. The expression of FasB mRNA was down-regulated when the cells were treated with TNFa and IFNg, but its expression was not changed by treatment with TNFa alone or IFNg alone. In conclusion, FasB inhibits apoptosis induction in luteal cells of normal luteal bodies, and decreased FasB production induced by TNFa and IFNg facilitated apoptosis induction in the luteal cells of regressing luteal bodies.
KEY WORDS: luteal body, apoptosis, tumor necrosis factor alpha, interferon gamma