2014
DOI: 10.1095/biolreprod.113.114215
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Impact of Obesity on Ovotoxicity Induced by 7,12-dimethylbenz[a]anthracene in Mice1

Abstract: 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 affect… Show more

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Cited by 30 publications
(57 citation statements)
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“…DMBA is an ovotoxicant that causes follicle depletion, ultimately resulting in ovarian failure (Keating et al ., 2008; Igawa et al ., 2009; Nteeba et al, 2014). This study was designed to focus on effects of DMBA on large primary and secondary follicles by allowing these follicles to develop in culture before DMBA exposure.…”
Section: Discussionmentioning
confidence: 99%
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“…DMBA is an ovotoxicant that causes follicle depletion, ultimately resulting in ovarian failure (Keating et al ., 2008; Igawa et al ., 2009; Nteeba et al, 2014). This study was designed to focus on effects of DMBA on large primary and secondary follicles by allowing these follicles to develop in culture before DMBA exposure.…”
Section: Discussionmentioning
confidence: 99%
“…In cultured rat pre-ovulatory follicles, co-treatment with GSH during DMBA exposure lessened follicle apoptosis (Tsai-Turton et al , 2007) suggesting the possible involvement of GST enzymes in catalyzing detoxification of DMBA. Gstpi has previously been identified to be involved in the ovarian response to DMBA exposure in neonatal rat ovaries (Bhattacharya and Keating, 2012), and adult mice exposed to DMBA (Nteeba et al ., 2014). Gstpi -null mice are also more sensitive to DMBA-induced skin tumors (Henderson et al ., 1998).…”
Section: Discussionmentioning
confidence: 99%
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“…Also, increased ovarian PI3K signaling and mEH have been demonstrated in mice fed a high fat diet until obese (Nteeba et al , 2013). The obese lethal yellow mouse was also found to have both higher basal levels of mEH and greater mEH induction in response to DMBA exposure (Nteeba et al , 2014). These data suggest that ovarian tissue from obese females could have potentially greater exposure to the ovotoxic metabolite of DMBA, due to higher levels of ovarian mEH, and thus greater DMBA bioactivation to a metabolite that interacts with DNA (Miyata et al , 1999).…”
Section: Introductionmentioning
confidence: 99%