Abstract
Sex-related differences in cardiovascular health and disease have been identified, with males having a higher incidence of cardiovascular events but females more likely to develop arrhythmias. Adverse fetal environments are now accepted as a cause for the development of cardiovascular diseases in adulthood, but sex-related differences in response to adverse fetal environments have not been extensively explored. The combination of both in utero and postnatal exposure to inflammation is highly relevant for the infant that is born preterm or has clinical complications at birth or in early postnatal life. We have previously observed cardiac contractile deficiencies and dysregulation of Ca2+-handling proteins in our model of maternal lipopolysaccharide (LPS) and neonatal hyperoxia exposures (LPS/O2). This investigation tested the hypothesis that there are sex-related differences in the adult pathologies after exposure to perinatal inflammation. Using pressure-volume assessments, males exposed to LPS/O2 had more pronounced contractile deficiencies than similarly exposed females, but females tended to have long PR intervals. While both sexes demonstrated decreases in α-myosin heavy chain and connexin 43 after LPS/O2 exposure compared with saline/room air controls, females indicated aberrant increases in microRNA 208a, microRNA 208b, and desmin expression. Our study supports our hypothesis that early life exposure to inflammation results in sex-dependent deficits in cardiovascular function. NEW & NOTEWORTHY Sex-specific differences in cardiovascular disease are recognized, but the mechanisms and origins are not well understood. Adverse maternal environments can influence cardiac development and later cardiovascular disease. This study identifies sex-dependent differences in cardiac disease associated with perinatal inflammation.