PMID- 26161038 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1445-5781 (Print) IS - 1447-0578 (Electronic) IS - 1445-5781 (Linking) VI - 14 IP - 3 DP - 2015 TI - Tumor necrosis factor alpha inhibits ovulation and induces granulosa cell death in rat ovaries. PG - 107-115 AB - PURPOSE: We evaluated the role of tumor necrosis factor alpha (TNFalpha) in rat ovulation and granulosa cell death of ovarian follicles during the periovulatory stage. METHODS: Immature rats primed with pregnant mare serum gonadotropin were injected intraperitoneally with human chorionic gonadotropin (hCG), and TNFalpha was injected into the bursa 48 h later. The total number of released oocytes was counted. Apoptosis was measured with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and the expression of cleaved caspase 3 and Bax/Bcl-2. Autophagy was assessed by the expression of light chain protein 3 (LC3) and autophagosomes under transmission electron microscopy. RESULTS: TNFalpha significantly decreased the number of released oocytes, and many unruptured follicles were observed. TUNEL analysis revealed a larger number of apoptotic cells, and the cleaved caspase 3 and Bax/Bcl-2 increased more than that of the control 12 h after hCG administration. Furthermore, the expression of LC3 wwas significantly higher than that of the control, and autophagosomes were observed in the cytoplasm. CONCLUSIONS: Our data indicated that TNFalpha is an important mediator of ovulation in terms of decreasing the number of released oocytes and inducing granulosa cell death of unruptured follicles via apoptosis and autophagy for remodeling ovarian tissues. FAU - Yamamoto, Yuri AU - Yamamoto Y AD - Department of Obstetrics and Gynecology, The University of Tokushima, Institute for Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503 Japan. FAU - Kuwahara, Akira AU - Kuwahara A AD - Department of Obstetrics and Gynecology, The University of Tokushima, Institute for Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503 Japan. FAU - Taniguchi, Yuka AU - Taniguchi Y AD - Department of Obstetrics and Gynecology, The University of Tokushima, Institute for Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503 Japan. FAU - Yamasaki, Mikio AU - Yamasaki M AD - Department of Obstetrics and Gynecology, The University of Tokushima, Institute for Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503 Japan. FAU - Tanaka, Yu AU - Tanaka Y AD - Department of Obstetrics and Gynecology, The University of Tokushima, Institute for Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503 Japan. FAU - Mukai, Yukari AU - Mukai Y AD - Department of Obstetrics and Gynecology, The University of Tokushima, Institute for Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503 Japan. FAU - Yamashita, Mizuho AU - Yamashita M AD - Department of Obstetrics and Gynecology, The University of Tokushima, Institute for Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503 Japan. FAU - Matsuzaki, Toshiya AU - Matsuzaki T AD - Department of Obstetrics and Gynecology, The University of Tokushima, Institute for Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503 Japan. FAU - Yasui, Toshiyuki AU - Yasui T AD - Department of Obstetrics and Gynecology, The University of Tokushima, Institute for Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503 Japan. FAU - Irahara, Minoru AU - Irahara M AD - Department of Obstetrics and Gynecology, The University of Tokushima, Institute for Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503 Japan. LA - eng PT - Journal Article DEP - 20141213 PL - Japan TA - Reprod Med Biol JT - Reproductive medicine and biology JID - 101213278 PMC - PMC4490172 OTO - NOTNLM OT - Apoptosis OT - Autophagy OT - Granulosa cell death OT - Ovulation OT - TNF-alpha COIS- Yuri Yamamoto, Akira Kuwahara, Yuka Taniguchi, Mikio Yamasaki, Yu Tanaka, Toshiya Matsuzaki, Toshiyuki Yasui, Minoru Irahara declare that they have no competing interests. EDAT- 2015/07/15 06:00 MHDA- 2015/07/15 06:01 PMCR- 2014/12/13 CRDT- 2015/07/11 06:00 PHST- 2014/06/27 00:00 [received] PHST- 2014/11/26 00:00 [accepted] PHST- 2015/07/11 06:00 [entrez] PHST- 2015/07/15 06:00 [pubmed] PHST- 2015/07/15 06:01 [medline] PHST- 2014/12/13 00:00 [pmc-release] AID - 201 [pii] AID - RMB20201 [pii] AID - 10.1007/s12522-014-0201-5 [doi] PST - ppublish SO - Reprod Med Biol. 2015;14(3):107-115. doi: 10.1007/s12522-014-0201-5. Epub 2014 Dec 13.