Soluble Fas (FasB) regulates luteal cell apoptosis during luteolysis in murine ovaries

• Published in: Molecular reproduction and development 2003-08, Vol.65 (4), p.345-352
• Main Authors: Komatsu, Kohji, Manabe, Noboru, Kiso, Minako, Shimabe, Munetake, Miyamoto, Hajime
• Format: Article
• Language: English
• Subjects: Animals; apoptosis; Apoptosis - drug effects; Biological and medical sciences; Cell Survival; Cells, Cultured; Corpus Luteum - chemistry; Corpus Luteum - cytology; Fas Ligand Protein; fas Receptor - genetics; fas Receptor - metabolism; fas Receptor - physiology; Female; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Hormone metabolism and regulation; Interferon-gamma - analysis; Interferon-gamma - pharmacology; luteal cell; Luteal Cells - drug effects; Luteal Cells - physiology; Luteal Cells - ultrastructure; Luteolysis; Mammalian female genital system; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Membrane Glycoproteins - pharmacology; Mice; Mice, Inbred ICR; mouse ovary; Ovary - chemistry; Recombinant Proteins - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Solubility; soluble Fas (FasB); Tumor Necrosis Factor-alpha - analysis; Tumor Necrosis Factor-alpha - pharmacology; Vertebrates: reproduction
• ISSN: 1040-452X; 1098-2795
• DOI: 10.1002/mrd.10312

During luteolysis, luteal cell apoptosis is induced by the Fas ligand (FasL)/Fas system. In murine luteal bodies, we demonstrated the expression of mRNA of 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 apoptotic cells were detected, but negative/trace expression in regressing luteal bodies, in which many apoptotic cells were observed. Immunohistochemical staining revealed that Fas and TNF‐α were localized in both normal and regressing luteal bodies, but IFN‐γ was localized only in regressing luteal bodies. Apoptosis was induced in primary cultured luteal cells, when they were pretreated with TNF‐α and IFN‐γ and then incubated with TNF‐α, IFN‐γ, and mouse recombinant FasL (rFasL). However, no apoptosis was detected in the cells, when they were treated with rFasL alone, TNF‐α alone, IFN‐γ alone, TNF‐α and rFasL, IFN‐γ and rFasL, or TNF‐α and IFN‐γ. Fas mRNA expression in cultured luteal cells was up‐regulated by the treatment of TNF‐α, IFN‐γ, or TNF‐α and IFN‐γ. The expression of FasB mRNA was down‐regulated, when the cells were treated with TNF‐α and IFN‐γ, but its expression was not changed by the treatment of TNF‐α alone or IFN‐γ alone. We conclude that FasB inhibits the apoptosis induction in luteal cells of normal luteal bodies, and that decreased FasB production induced by TNF‐α and IFN‐γ made possible the apoptosis induction in the luteal cells of regressing luteal bodies. Mol. Reprod. Dev. 65: 345–352, 2003. © 2003 Wiley‐Liss, Inc.