Induction of Apoptosis by 9,10-Dimethyl-1,2-Benzanthracene in Cultured Preovulatory Rat Follicles Is Preceded by a Rise in Reactive Oxygen Species and Is Prevented by Glutathione

Details

• Personal Author:
  Luderer U ; Nakamura BN ; Tsai-Turton M
• Description:
  The polycyclic aromatic hydrocarbon (PAH) 9,10-dimethyl-1,2-benzanthracene (DMBA) destroys primordial, primary, and secondary ovarian follicles in rodents, but its effects on antral follicles have received limited attention. PAHs are metabolized to reactive species, some of which can undergo redox cycling to generate reactive oxygen species (ROS). We previously showed that ROS initiate apoptosis in preovulatory follicles cultured without gonadotropin support and that glutathione (GSH) depletion induces apoptosis in the presence of gonadotropins. In the present study, we tested the hypothesis that DMBA induces apoptosis in preovulatory follicles, which is mediated by ROS and prevented by GSH. Preovulatory follicles were isolated from ovaries of 25-day-old rats 48 h after the injection of 10 IU of eCG and were cultured with DMBA in the presence of FSH for 2 to 48 h. DMBA induced granulosa cell (GC) and theca cell (TC) apoptosis at 48 h, as judged by TUNEL and activated caspase-3 immunostaining. DMBA treatment also increased the numbers of GCs and TCs that immunostained for the proapoptotic protein BAX. Follicular ROS levels were significantly increased in DMBA-treated follicles at 12, 24, and 48 h. GSH supplementation protected against and GSH depletion enhanced the induction of apoptosis in GCs and TCs by DMBA. These findings suggest that GSH is a critical protective mechanism against DMBA-induced apoptosis in antral follicles and that ROS generation may mediate DMBA-induced GC apoptosis. [Description provided by NIOSH]
• Subjects:
  Antioxidants Hydrocarbons Occupational Health Polycyclic Aromatic Hydrocarbons Safety Urogenital System
• Keywords:
  Atresia Author Keywords: Apoptosis Cellular Effects Dimethylbenzanthracene Follicle Glutathione Oxidative Stress Polycyclic Aromatic Hydrocarbon Polycyclic Aromatic Hydrocarbons Reactive Oxygen Species Reproductive Effects ROS Toxicology

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• ISSN:
  0006-3363
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  442-451
• Volume:
  77
• Issue:
  3
• NIOSHTIC Number:
  nn:20058476
• Citation:
  Biol Reprod 2007 Sep; 77(3):442-451
• Contact Point Address:
  Ulrike Luderer, Center for Occupational and Environmental Health, 5201 California Avenue, Suite 100, Irvine, CA 92617
• Email:
  uluderer@uci.edu
• CAS Registry Number:
  Glutathione (CAS RN 70-18-8)
• Federal Fiscal Year:
  2007
• Performing Organization:
  University of California Los Angeles
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Biology of Reproduction
• End Date:
  20270630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ec2c6927828cd4b699ebe2ba4642eb7cde83971cf180251e2ab665c05eb9a8901af0efca8c2e9dfef16f316c4be41d1b5cfd4a2b5c7fe2b6c899678fb44541e2
• Download URL:
  https://stacks.cdc.gov/view/cdc/221565/cdc_221565_DS1.pdf
• File Type:
  [PDF - 585.20 KB ]