Abstract
BACKGROUND: Suppressing estradiol (E(2)) during baboon pregnancy lowers offspring skeletal muscle capillary density, vital for insulin-mediated glucose uptake, and induces insulin resistance. We examined whether E(2) deprivation also impairs microvascular flow and cardiac function. METHODS: Offspring of untreated baboons, letrozole-treated baboons, or letrozole plus E(2) (maternal s.c. injections during the second half of gestation) underwent contrast-enhanced microbubble ultrasonography to quantify microvessel flow and echocardiography to assess cardiac performance. RESULTS: Letrozole reduced maternal serum E(2) by 95% (p < 0.01). In letrozole offspring, microbubble flux rate (β) fell 55% (p < 0.02), replenishment was 5 s slower (p < 0.03), and microvessel flow declined 40% (p = 0.05); all were restored by added E(2). Indices of systolic (isovolumic contraction), diastolic (isovolumic relaxation), global performance (Tei index), and cardiac output were unchanged. CONCLUSION: Prolonged gestational E(2) deprivation programs a reduction in microvascular flow without altering cardiac function; maternal E(2) prevents this, supporting E(2)'s role in optimizing postnatal perfusion and metabolic health.