Estrogen and progesterone play pivotal roles in endothelial progenitor cell proliferation

The number of EPCs in peripheral blood from subjects in the menstrual phase (n = 12), follicular phase (n = 8), and luteal phase (n = 16), was measured using flow cytometry. Peripheral blood mononuclear cells (PBMCs) were cultured for seven days with or without 17beta-estradiol (E2beta) or P4, followed by assessment of EPC proliferation based upon the uptake of acetylated low density lipoprotein (LDL) and lectin. The expression of estrogen receptor (ER) or progesterone receptor (PR) in EPCs was also evaluated using real-time PCR.E2beta and P4 significantly increased the proliferation of EPCs derived from the peripheral blood of subjects in menstrual phase, but not subjects in the luteal phase. In addition, the expression level of ERalpha was markedly higher than ERbeta in EPCs derived from women in menstrual phase.EPC proliferation is induced during the menstrual phase and proliferation can be affected by estrogen through ERalpha activation.Angiogenesis in female reproductive organs, including the uterus, corpus luteum, and placenta, is essential for implantation and is critical for the dramatic (30-50 fold) elevation of uterine blood flow during pregnancy [1,2]. Disturbances in uterine vascular development are associated with pregnancy loss, preeclampsia, and intrauterine growth restriction [3]. Periodic uterine endometrial neovascularization begins after menstruation and continues into the luteal phase [4]. In general, it is thought that neovascularization is mainly caused by angiogenesis, which is the sprouting of capillaries from pre-existing vessels, such as in tumors and embryos. However, vasculogenesis, which is mediated by endothelial progenitor cells (EPCs), has recently been proposed to be involved in endometrial neovascularization [5,6]. The presence of EPCs in peripheral blood provides a maintenance reservoir of endothelial cells (ECs) and contributes to up to 25% of ECs in newly formed vessels [7]. It has been hypothesized that EPCs may be involved in t