HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 77/3/442    most recent biolreprod.107.060368v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal My Folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tsai-Turton, M. Articles by Luderer, U. Search for Related Content PubMed PubMed Citation Articles by Tsai-Turton, M. Articles by Luderer, U. Agricola Articles by Tsai-Turton, M. Articles by Luderer, U.

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 Glutathione¹

Departments of Community and Environmental Medicine,³ Medicine,⁴ and Developmental and Cell Biology,⁵ University of California Irvine, Irvine, California 92617

ABSTRACT

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.

apoptosis, atresia, dimethylbenzanthracene, follicle, glutathione, oxidative stress, polycyclic aromatic hydrocarbon, toxicology

¹Supported by NIH grant K08 ES10963 (to U.L), the University of California Irvine Developmental Biology Center and Chao Family Comprehensive Cancer Center Optical Biology Shared Resource (NIH Cancer Center Support grant P50 CA62203), and the Center for Occupational and Environmental Health, University of California, Irvine.

Correspondence: ²Ulrike Luderer, Center for Occupational and Environmental Health, 5201 California Ave., Suite 100, Irvine, CA 92617. FAX: 949 824 2345; e-mail: uluderer{at}uci.edu

This article has been cited by other articles:

				C. Ortega-Camarillo, A. Gonzalez-Gonzalez, M. Vergara-Onofre, E. Gonzalez-Padilla, A. Avalos-Rodriguez, M. E Gutierrez-Rodriguez, L. Arriaga-Pizano, M. Cruz, L. A. Baiza-Gutman, and M. Diaz-Flores Changes in the glucose-6-phosphate dehydrogenase activity in granulosa cells during follicular atresia in ewes Reproduction, June 1, 2009; 137(6): 979 - 986. [Abstract] [Full Text] [PDF]

				M. M. Cortes-Wanstreet, E. Giedzinski, C. L. Limoli, and U. Luderer Overexpression of glutamate-cysteine ligase protects human COV434 granulosa tumour cells against oxidative and {gamma}-radiation-induced cell death Mutagenesis, May 1, 2009; 24(3): 211 - 224. [Abstract] [Full Text] [PDF]