The online version of this article (doi:10.1186/1477-7827-10-2) contains supplementary material, which is available to authorized users.
and Keiichi Matsubara contributed equally to this work.
The authors declare that they have no competing interests.
YM collected all samples, carried out the molecular genetic studies, participated in the sequence alignment, and drafted the manuscript. KM carried out EPC isolation, LDL/lectin assay, and FACS analysis. KM also participated in the design of the study, performed the statistical analysis, and helped to review the manuscript. All authors read and approved the final manuscript.
It has been previously suggested that angiogenesis occurs during the menstrual cycle. Moreover, a rise in uterine blood flow is largely maintained by vasodilatation and substantial increases in angiogenesis. It is known that estradiol (E2) and progesterone (P4) are involved in angiogenesis. Recently, endothelial progenitor cells (EPCs) were found to be involved in neovascularization; however, their roles in uterine neovascularization have not been well characterized. We hypothesized that E2- or P4-mediated EPC proliferation plays important roles in uterine neovascularization during the menstrual cycle.
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.
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