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-beta and agonist and antagonist of ER-alpha) and (R, R)-5,11-diethyl-5,6,11,12-tetrahydro-2,8-chrysenediol (THC; an agonist of ER-alpha and antagonist of ER-beta) 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-beta-estradiol (10(-9) and 10(-10) M) significantly inhibited migration in female EPCs but not in males. Moreover, both 10(-5) M THC and 10(-8) M BPA blocked migration in female EPCs, allowing us to hypothesize that the effect is mediated by ER-alpha. 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. (C) 2016 S. Karger AG, Basel