title: Tumor necrosis factor alpha inhibits ovulation and induces granulosa cell death in rat ovaries.
abstract: OBJECTIVE
  We evaluated the role of tumor necrosis factor alpha (TNFα) 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 TNFα 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
  TNFα 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 TNFα 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.
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima, Institute for Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503 Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima, Institute for Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503 Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kuwahara
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima, Institute for Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503 Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Taniguchi
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima, Institute for Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503 Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Yamasaki
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima, Institute for Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503 Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima, Institute for Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503 Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Mukai
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima, Institute for Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503 Japan.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Yamashita
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima, Institute for Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503 Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Matsuzaki
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima, Institute for Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503 Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yasui
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima, Institute for Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503 Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Irahara
keywords: Apoptosis; Autophagy; Granulosa cell death; Ovulation; TNF-alpha