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Hum. Reprod. Advance Access published online on December 16, 2008
Human Reproduction, doi:10.1093/humrep/den411
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Influence of menstrual cycle on circulating endothelial progenitor cells

A.O. Robb1, N.L. Mills2, I.B.J. Smith1, A. Short1, O. Tura-Ceide3, G.R. Barclay3, A. Blomberg4, H.O.D. Critchley1, D.E. Newby2 and F.C. Denison1,5

1 Centre for Reproductive Biology, University of Edinburgh, Edinburgh EH16 4TJ, UK 2 Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh EH16 4TJ, UK 3 Scottish Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4SB, UK 4 The Department of Respiratory and Allergy Medicine, University Hospital, Umea, Sweden

5 Correspondence address. The Simpson Centre for Reproductive Health The Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, UK. Tel: +44-131-242-2692; Fax: +44-131-242-2686; E-mail: fiona.denison{at}ed.ac.uk

BACKGROUND: Endothelial progenitor cells (EPCs) are circulating mononuclear cells that participate in angiogenesis. The aim of this study was to determine the influence of the menstrual cycle on the number and function of EPCs, and to investigate their relationship with circulating concentrations of sex steroids and inflammatory mediators.

METHODS: Ten healthy nulliparous, premenopausal, non-smoking women with regular menses were studied over a single menstrual cycle. Venepuncture was performed in the menstrual, follicular, peri-ovulatory and luteal phases. EPCs were quantified by flow cytometry (CD133+CD34+KDR+ phenotype) and the colony-forming unit (CFU-EPC) functional assay. Circulating concentrations of estradiol, progesterone and inflammatory mediators (TNF-{alpha}, IL-6, sICAM-1 and VEGF) were measured by immunoassays.

RESULTS: The numbers of CD133+CD34+KDR+ cells were higher in the follicular phase (0.99 ± 0.3 x 106 cells/l) compared with the peri-ovulatory phase (0.29 ± 0.1 x 106 cells/l; P < 0.05). In contrast, the numbers of CFU-EPCs did not vary over the menstrual cycle. There were no correlations between EPCs and concentrations of either circulating sex steroids or inflammatory mediators.

CONCLUSIONS: CD133+CD34+KDR+ cells but not CFU-EPCs vary during the menstrual cycle. Our findings suggest a potential role for circulating EPCs in the normal cycle of physiological angiogenesis and repair of the uterine endometrium that is independent of circulating sex steroids or inflammatory mediators.

Key words: enothelial progenitor cells/menstrual cycle/angiogenesis/endometrium

Submitted on May 23, 2008; resubmitted on September 10, 2008; accepted on September 18, 2008.


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