Altered histone abundance as a mode of ovotoxicity during 7,12-dimethylbenz[a]anthracene exposure with additive influence of obesity

The objective of this study was to identify ovarian proteomic and histone modifications induced by DMBA exposure and to examine any influence of obesity thereon. Post-pubertal wildtype (KK.Cg-a/a; lean) and agouti (KK.Cg-Ay/J; obese) female mice, were exposed to either corn oil (CT) or DMBA (1 mg/kg) for 7d via intraperitoneal injection (n = 10/treatment). Total ovarian proteome analysis (LC-MS/MS) determined that obesity altered a total of 225 proteins (P < 0.05) and histone 3 was the second least abundant protein (FC = -5.98, P < 0.05). Histone 4 was decreased by 3.33-fold whereas histone variant H3.3 was decreased by 3.05-fold and variants H1.2, H1.4 and H1.1(alpha) were increased by 1.59, 1.90 and 2.01-fold, respectively (P < 0.05). DMBA exposure altered 48 proteins in lean mice but no alterations in histones or histone variants were observed. In obese mice, DMBA exposure altered 120 proteins and histone 2B abundance was increased by 0.30-fold (P < 0.05). In DMBA-exposed mice, obesity altered the abundance of 634 proteins. Histones 4, 3 and 2A type 1-F were decreased by 4.03, 3.71, 0.43-fold, respectively, whereas histone variant H1.2 and linker histone, H15 were increased by 2.72- and 3.07-fold, respectively (P < 0.05). Thus, histones and histone variants respond to DMBA exposure, and this response is more pronounced during obesity, potentially altering ovarian transcriptional regulation.PMID:37856498 | DOI:10.1093/biolre/ioad140
Source: Biology of Reproduction - Category: Reproduction Medicine Authors: Source Type: research