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The ovotoxicant, dimethylbenz[a]anthracene, is biotransformed into a genotoxic metabolite to which the ovary responds by activating the ataxia telangiectasia mutated DNA repair pathway. Basal ovarian DNA damage coupled with a blunted response to genotoxicant exposure occurs in obese females, leading to the hypothesis that obesity potentiates ovotoxicity through ineffective DNA damage repair. Female KK.Cg-a\/a (lean) and KK.Cg-Ay\/J (obese) mice received corn oil or dimethylbenz[a]anthracene (1\u00a0mg\/kg) at 9 weeks of age for 7 days via intraperitoneal injection (n\u2009=\u200910\/treatment). Obesity increased liver weight (P\u2009&amp;lt;\u20090.001) and reduced (P\u2009&amp;lt;\u20090.05) primary, preantral, and corpora lutea number. In lean mice, dimethylbenz[a]anthracene exposure tended (P\u2009&amp;lt;\u20090.1) to increase proestrus duration and reduced (P\u2009=\u20090.07) primordial follicle number. Dimethylbenz[a]anthracene exposure decreased (P\u2009&amp;lt;\u20090.05) uterine weight and increased (P\u2009&amp;lt;\u20090.05) primary follicle number in obese mice. Total ovarian abundance of BRCA1, \u03b3H2AX, H3K4me, H4K5ac, H4K12ac, and H4K16ac (P\u2009&amp;gt;\u20090.05) was unchanged by obesity or dimethylbenz[a]anthracene exposure. Immunofluorescence staining demonstrated decreased (P\u2009&amp;lt;\u20090.05) abundance of \u03b3H2AX foci in antral follicles of obese mice. In primary follicle oocytes, BRCA1 protein was reduced (P\u2009&amp;lt;\u20090.05) by dimethylbenz[a]anthracene exposure in lean mice. Obesity also decreased (P\u2009&amp;lt;\u20090.05) BRCA1 protein in primary follicle oocytes. These findings support both a follicle stage-specific ovarian response to dimethylbenz[a]anthracene exposure and an impact of obesity on this ovarian response.<\/jats:p>","DOI":"10.1093\/biolre\/ioac218","type":"journal-article","created":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T02:44:00Z","timestamp":1674787440000},"page":"694-707","source":"Crossref","is-referenced-by-count":10,"title":["Obesity partially potentiates dimethylbenz[a]anthracene-exposed ovotoxicity by altering the DNA damage repair response in mice"],"prefix":"10.1093","volume":"108","author":[{"given":"Jaspreet K","family":"Rishi","sequence":"first","affiliation":[{"name":"Department of Animal Science, Iowa State University , Ames, IA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelsey","family":"Timme","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Iowa State University , Ames, IA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hunter E","family":"White","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Iowa State University , Ames, IA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl C","family":"Kerns","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Iowa State University , Ames, IA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aileen F","family":"Keating","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Iowa State University , Ames, IA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,1,25]]},"reference":[{"key":"2023041705194878600_","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1517\/17425255.2014.880690","article-title":"Xenobiotic effects in the ovary: temporary versus permanent 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