Ovarian SUMO-2/3 targets and their differential response to genotoxic stress induced by 7,12-dimethylbenz(a)anthracene exposure in lean and obese female mice.

Abstract

SUMOylation is a post-translational modification critical for oocyte development and chromatin-associated processes. Environmental exposures and obesity can cause follicle depletion and exposure to 7,12-dimethylbenz(a)anthracene (DMBA) altered ovarian SUMO protein abundance in lean and obese mice. Thus, the hypothesis that exposure to DMBA may alter ovarian protein SUMOylation as a mode of ovotoxicity dampened by obesity was tested. Lean and obese mice (KK.Cg-a/a and KK.Cg-Ay/J) were exposed to either corn oil or DMBA (1 mg/kg) intraperitoneally for 7d (n = 4/treatment) and ovaries were flash-frozen on the second day of diestrus. Protein was isolated followed by immunoprecipitation using a SUMO-2/3 antibody and precipitated proteins were identified via liquid chromatography-tandem mass spectrometry. A total of 114 SUMO-2/3 ovarian protein targets were identified. Obesity basally altered (P ≤ 0.05) the abundance of 55 SUMOylated proteins with an additional 11 proteins tending (P ≤ 0.1) to be altered. In lean mice, DMBA altered (P < 0.05) the level of SUMOylation profile of 18 proteins with an additional three proteins tending (P ≤ 0.1) to be changed by DMBA exposure. In obese mice, DMBA exposure altered (P < 0.05) the abundance of 29 SUMOylated proteins and seven proteins had a tendency towards being different (P ≤ 0.1). DMBA exposure of lean compared to obese mice affected (P < 0.05) SUMOylation of 43 proteins, and four additional proteins tended (P ≤ 0.1) to differ. These findings suggest that protein SUMOylation is a mode of ovotoxicity which is influenced by physiological status.