Prenatal Androgen Exposure of Single‐Injection of Testosterone Induces Cardiovascular and Metabolic Dysfunction in Adult Female Wistar Rats.

Abstract

Cardiovascular disease is the leading cause of death in men and women within the United States. Individuals at risk for developing cardiovascular disease possess morbidity characteristic of metabolic dysfunction including diabetes, hypertension, and obesity. Previous studies have found that the origins of cardiovascular disease may arise from the prenatal environment and exposure to excess sex steroids such as testosterone produces adverse consequences that place male and female adult offspring at risk for the development of insulin resistance, infertility, obesity, and heart disease. However, the effects of excess testosterone on female cardiovascular function remains poorly understood. In this study, we hypothesized that a single‐injection of testosterone in the late gestation of Wistar rats would establish a metabolic phenotype characteristic of hypertension in adult female rats. Sixty‐six female Wistar rats were separated into two groups, vehicle and prenatal androgen (PNA), after weaning. We investigated the effect of excess testosterone on cardiovascular function and morphology with telemetry, echocardiogram, and immunohistochemistry. We also assessed insulin and glucose tolerance and utilized quantitative gene expression analysis to determine differential gene and protein expression. Our data suggest that the prenatal exposure to excess androgen alters systemic expression of genetic markers associated with diabetes and hypertension and negatively impacts cardiovascular function by increasing systolic and diastolic blood pressure. Overall, our results confirm that prenatal androgen exposure may negatively impact cardiovascular health of females in adulthood.