Expression and Function of Apoptosis Initiator FOXO3 in Granulosa Cells During Follicular Atresia in Pig Ovaries
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概要
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In mammalian ovaries, most follicles are lost by atresia before ovulation. It has become apparent that the apoptosis of granulosa cells induces follicular atresia. Forkhead box O3 (FOXO3), also called FKHRL1 (forkhead in rhabdomyosarcoma-like 1), is a proapoptotic molecule that belongs to the FOXO subfamily of forkhead transcription factors. Foxo3-deficient female mice were reported to be infertile because of abnormal ovarian follicular development, but the precise influences of FOXO3 on follicular atresia of mature ovary have not been determined. Therefore, we examined the expression and function of FOXO3 in porcine ovarian follicles and granulosa-derived cells. FOXO3 mRNA levels in granulosa cells of porcine ovaries increased during atresia, while FOXO3 protein was abundant in granulosa cells of early atretic follicles. By immunohistochemistry, the inner surface area of the granulosa layer in early atretic follicles was strongly stained with anti-FOXO3 antibody. The granulosa cells expressing FOXO3 coincided with apoptotic cells, indicating a role of FOXO3 as a proapoptotic factor in granulosa cells of porcine ovaries. In porcine (JC-410) and human (KGN) granulosa-derived cells, cell death was induced by transfection of FOXO3 expression vectors. Expression of the proapoptotic factors Fas ligand (FASLG) and BCL2-like 11 (BCL2L11) was upregulated by FOXO3 in KGN cells. In conclusion, FOXO3 is expressed in porcine ovarian follicles and induces apoptosis in granulosa cells, suggesting that it is a candidate for the initiator of follicular atresia.
著者
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MANABE Noboru
Research Unit of Animal Life Sciences, Animal Resource Science Centre, The University of Tokyo
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Inoue Naoko
Laboratory Of Animal Morphology And Function Graduate School Of Bioagricultural Sciences Nagoya Univ
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MAEDA Akihisa
Research Unit for Animal Life Sciences, Animal Resource Science Center, The University of Tokyo
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SAKAMAKI Kazuhiro
Laboratory of Tumore Cell Biology, Department of Life Sciences, Kyoto University
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MATSUDA Fuko
Research Unit for Animal Life Sciences, Animal Resource Science Center, Graduate School of Agricultu
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GOTO Yasufumi
Research Unit for Animal Life Sciences, Animal Resource Science Center, Graduate School of Agricultu
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CHENG Yuan
Research Unit for Animal Life Sciences, Animal Resource Science Center, Graduate School of Agricultu
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SAI Takafumi
Research Unit for Animal Life Sciences, Animal Resource Science Center, Graduate School of Agricultu
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GONDA Hiroshi
Research Unit for Animal Life Sciences, Animal Resource Science Center, Graduate School of Agricultu
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