Background: Alcohol exposure during pregnancy is known to impair cardiac development by altering cardiomyocyte maturation and increasing fibrosis1. While many women stop drinking at pregnancy recognition, alcohol consumption during the periconceptional period (PC) is common. This study aimed to examine mechanisms which may lead to cardiac dysfunction following periconceptional alcohol exposure, with emphasis on sex-specific effects. We hypothesised that cardiac dysfunction in response to periconceptional alcohol exposure (PC:EtOH) would be associated with altered expression of estrogen regulated genes.
Methods: Sprague Dawley rats were given either a control liquid diet or 12.5%v/v ethanol diet from four days before mating until four days after mating (PC:EtOH). At 12-14 months, offspring underwent echocardiography to assess heart function. Left ventricle (LV) samples were dissected at 18 months and snap frozen before expression levels of estrogen receptor alpha (ESR1), heat shock protein 90 (HSP90a) and GLUT4 (Slc2A4) were measured via qPCR. HSP90a was analysed using western blot.
Results: Female PC:EtOH offspring had increased left ventricular internal diameter during systole (LVIDs, P<0.05), reduced cardiac output (P<0.05) and a trend toward reduced fractional shortening (P=0.08). Male offspring, however, had normal heart function. PC:EtOH increased LV expression of ESR1 (PTrt<0.05), predominantly in female offspring (P<0.05). PC:EtOH increased expression of HSP90a (PInt<0.05) with post hoc analysis indicating an increase in females only (P<0.01). PC:EtOH had no effect on protein levels of HSP90a, nor Slc2A4 mRNA expression.
Conclusion: This study is the first to show that a periconceptional influence can have lasting effects on cardiac expression of ESR1 and HSP90a, which maintains ESR1 in an active form. These results suggest that cardiac dysfunction seen in periconceptional alcohol-exposed female offspring may be due to alterations in estrogen. Given this potential increased risk of cardiovascular disease, it is important that women cease consuming alcohol when planning a pregnancy.