Estrogenic Compounds Have Divergent Effects on Human Endothelial Progenitor Cell Migration according to Sex of the Donor

BACKGROUND: Endothelial progenitor cells (EPCs) are key elements in vascular homeostasis. Their function is regulated by estrogens and estrogen receptors (ERs), but the effect of estrogenic compounds such as bisphenol A (BPA; an agonist of ER-β and agonist and antagonist of ER-α) and (R,R)-5,11-diethyl-5,6,11,12-tetrahydro-2,8-chrysenediol (THC; an agonist of ER-α and antagonist of ER-β) on human EPCs is unknown. We analyzed whether BPA and THC influence the migration of human EPCs, an essential process in endothelial regeneration, in both male and female EPCs. METHODS: EPCs isolated from healthy adult men and women were assayed for ER expression by Western blotting and chemotaxis assay. RESULTS: Male and female EPCs similarly expressed ERs and did not differ in basal migration. Interestingly, 17-β-estradiol (10-9 and 10-10M) significantly inhibited migration in female EPCs but not in males. Moreover, both 10-5M THC and 10-8M BPA blocked migration in female EPCs, allowing us to hypothesize that the effect is mediated by ER-α. CONCLUSIONS: Estrogenic compounds have a sex divergent effect which could help in understanding differences in the pathophysiology of endothelial function observed between men and women.