Cardiovascular diseases and diabetes are the leading cause of mortality and morbidity in the US. Hypertension affects 1 in 3 and diabetes affects 1 in 10 adults—in the US. The pathogenesis of high blood pressure and diabetes are unclear, and consequently, treatment is symptomatic rather than treating the underlying cause.
According to a new field of research, what happens during pregnancy can have lasting consequences that emerge decades after the child leaves the hospital. Much of what a pregnant woman encounters in her daily life — 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. We have shown that eating a low protein diet, smoking, or drinking alcohol during pregnancy suppresses fetal growth and leads to adult-onset hypertension.
We found that unhealthy habits and disease during pregnancy (i.e. stress, smoking, drinking alcohol, hypoxia, infection, etc) somehow triggers increase in testosterone levels — the hormone that was once thought to have significance only in males. When the fetus gets too much of testosterone, depending on the sex of the baby, their body organs will undergo what is called “programming”. The fetus will try to adjust in a way that will give them a survival advantage. But that modifies their gene expression for life in ways that may not in fact be advantageous leading to development of hypertension and diabetes.
We believe that prenatal testosterone effects are regarded as organizing the structure or architecture of the body and heart, and the distribution of hormone receptors, into a relatively male-like configuration. When testosterone increases later in life, it activates these preexisting structures. Thus, we believe diseases derive from the interaction of long-term organizational and shorter-term activational effects. An understanding of these organizational and activational mechanisms will provide an opportunity to prevent the development of adult-life diseases at the very origin, providing a novel approach of bringing preventive medicine back into the womb.
Future studies will be done with the following specific objectives:
1) Understand how elevated testosterone in the mother induces organizational and structural changes in the body and heart of the fetus;
2) Evaluate how testosterone activates sex-specific onset and severity of hypertension and examine the underlying signaling mechanisms in heart and vasculature;
3) Develop nutritional and pharmacologic therapeutic strategies that will have a practical clinical potential for prevention and treatment of abnormal maternal vascular adaptations and programming of organ function.