A woman’s body undergoes many changes at the onset of pregnancy. The most profound effects are observed in the cardiovascular system where blood volume increases by 50%, heart rate increases by 10-15 beats per minute, cardiac output increases by 30-50%, blood pressure decreases by 10-15 mm Hg, and hematocrit level decreases. These physiologic changes are essential to meet the nutritional and metabolic demands of her developing fetus. Hypertensive disorder of pregnancy, called preeclampsia, occur when these cardiovascular adjustments fail to reach optimal levels. A pregnant woman’s daily environment — the air she breathes, the food and drink she consumes, her weight and fitness, the chemicals and infections she is exposed to, even the emotions she feels — is shared in some fashion with her fetus. When the mother develops hypertension, the fetus responds by undergoing what is called “programming” whereby the fetus modifies its gene expression in way that will give them a survival advantage. In the long run, these modifications are in fact not advantageous, and have been found to lead to hypertension and diabetes during adulthood. These programming effects differ between male and female fetuses and activate sex-specific hypertensive and/or diabetic mechanisms. Our laboratory is interested in understanding the physiological and pathophysiological mechanisms underlying blood pressure control during pregnancy and the fetal origins of adult hypertension and diabetes. We use an integrated approach that combines basic science, molecular laboratory techniques, and state-of-the-art cardiovascular tools to study:
a) The mechanisms that contribute to normal cardiovascular adaptations to pregnancy -- with focus on steroid hormones and renin-angiotensin system.
b) Why these cardiovascular changes are perturbed in some pregnant women, and if lifestyle choices and disease(s) during pregnancy (i.e. endocrine disruption, stress, smoking, drinking alcohol, hypoxia, infection, etc.) play a role.
c) How disorders in the mother induce organizational and structural changes in the heart and vasculature of the fetus -- with a focused look at the roles of adrenal and gonadal hormones, genes, and inflammatory factors.
d) How the mechanisms of hypertension and diabetes differ between males and females with focus on the endothelium and vascular smooth muscle signaling.
An understanding of these pregnancy and fetal mechanisms will help to prevent abnormal maternal vascular function and the consequent development of adult diseases. This study provides a novel approach to bring preventive medicine into the womb. Further, understanding the sex effects in hypertension and diabetes will provide knowledge for the development of sex-specific treatments for these disorders.