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

J Vasc Res. 2015;52(4):273-8. doi: 10.1159/000443403. Epub 2016 Feb 9.

Abstract

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(-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-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.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Cells, Cultured
  • Chemotaxis / drug effects*
  • Dose-Response Relationship, Drug
  • Endothelial Progenitor Cells / drug effects*
  • Endothelial Progenitor Cells / metabolism
  • Estrogen Receptor alpha / agonists*
  • Estrogen Receptor alpha / metabolism
  • Estrogen Receptor beta / agonists*
  • Estrogen Receptor beta / metabolism
  • Estrogens / pharmacology*
  • Female
  • Humans
  • Male
  • Sex Factors
  • Signal Transduction / drug effects
  • Young Adult

Substances

  • ESR1 protein, human
  • ESR2 protein, human
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Estrogens