Sexually dimorphic effects of in-utero exposure to a real-life environmental chemical mixture on markers of cardiovascular function in adult sheep

Cardiovascular disease (CVD) is a major sexually dimorphic cause of mortality and morbidity. Prenatal exposure to environmental chemicals (ECs) can program the adult onset of CVD. Using a real-life EC exposure sheep model, this study investigated structural and molecular underpinnings of the sex-specific effects of prenatal EC mixture exposure via mothers grazing on biosolids treated pasture (BTP) in left ventricular (LV) tissues. EC mixture exposure had no impact on plasma TG and TC levels, LV cardiomyocyte number or collagen scoring in both sexes. However, a significant increase (P<0.05) in fibrosis was evident in interstitial, perivascular and replacement fibrosis in BTP males. A significant upregulation of inflammatory (MHC-DRB1, MHC-DYA), apoptosis (CASP3) markers, together with elevated IGF-1 and IGF1-R expression was restricted to EC exposed males only. These findings extend our earlier results on sex-specific differences in prenatal EC exposure programming of adult CV functioning, particularly in males.