Campus Units

Animal Science

Document Type


Publication Version

Accepted Manuscript

Publication Date


Journal or Book Title

Biology of Reproduction





First Page





Insulin, elevated during obesity, regulates xenobiotic biotransformation enzymes, potentially through phosphatidylinositol 3-kinase (PI3K) signaling, in extraovarian tissues. PI3K regulates oocyte viability, follicular activation, and ovarian chemical biotransformation. 7,12-Dimethylbenz[a]anthracene (DMBA), a carcinogen and ovotoxicant, destroys all stages of follicles, leading to premature ovarian failure. Obesity has been reported to promote DMBA-induced tumors, but it remains unknown whether obesity affects ovarian xenobiotic metabolism. Therefore, we investigated ovarian expression of xenobiotic metabolism genes—microsomal epoxide hydrolase (Ephx1), glutathione S-transferase (GST) class Pi (Gstp1) and class mu 1 (Gstm1), and PI3K-signaling members (protein kinase B [AKT] alpha [Akt1], beta [Akt2], and the forkhead transcription factor subfamily 3 [Foxo3])—in lean and obese female mice after DMBA exposure (1 mg/kg; intraperitoneal injection for 14 days). Relative to lean, obese mice had decreased (P , 0.05) healthy primordial and primary follicle numbers but increased (P , 0.05) secondary and preovulatory follicles numbers. Obesity increased (P , 0.05) Akt1, Akt2, Gstm1, and Ephx1 mRNA and pAKTSer473/Thr308, GSTM1, GSTP1, and EPHX1 protein levels. DMBA decreased (P , 0.05) ovarian weight in lean and obese mice, however, obese DMBA-treated females had a greater reduction (P , 0.05) in ovarian weight. In both lean and obese mice, DMBA decreased (P , 0.05) all stages of healthy follicle numbers, increased Gstp1 and Ephx1 mRNA as well as GSTM1, GSTP1, and EPHX1 protein levels, and decreased Akt1 and Akt2 mRNA as well as pAKTSer473 or pAKTThr308, FOXO3, and pFOXO3Ser253 protein expression. There was an additive effect between obesity and DMBA exposure for increased Gstm1 and Ephx1 mRNA as well as GSTM1 and EPHX1 protein expression.


This is a manuscript of an article published as Nteeba, Jackson, Shanthi Ganesan, and Aileen F. Keating. "Impact of obesity on ovotoxicity induced by 7, 12-dimethylbenz [a] anthracene in mice." Biology of reproduction 90, no. 3 (2014): 68. doi: 10.1095/biolreprod.113.114215. Posted with permission.

Copyright Owner

Society for the Study of Reproduction, Inc.



File Format


Published Version