• Open Access

Uterine Vasculature Remodeling in Human Pregnancy Involves Functional Macrochimerism by Endothelial Colony Forming Cells of Fetal Origin§

Authors

  • Peter I. Sipos,

    1. Maternal and Fetal Health Research Centre, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom
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  • Willem Rens,

    1. Department of Veterinary Medicine, Cambridge Veterinary School, University of Cambridge, Cambridge, United Kingdom
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  • HÉlène Schlecht,

    1. National Genetics Reference Laboratory (Manchester), St Mary's Hospital, Manchester, United Kingdom
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  • Xiaohu Fan,

    1. Department of Pediatrics and Pharmacology, University of Alberta, Edmonton, Alberta, CanadaUniversity of Alberta, Edmonton, Alberta, Canada
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  • Mark Wareing,

    1. Maternal and Fetal Health Research Centre, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom
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  • Christina Hayward,

    1. Maternal and Fetal Health Research Centre, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom
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  • Carl A. Hubel,

    1. Magee-Women's Research Institute and Department Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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  • Stephane Bourque,

    1. Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada
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  • Philip N. Baker,

    1. Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada
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  • Sandra T. Davidge,

    1. Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada
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  • Colin P. Sibley,

    1. Maternal and Fetal Health Research Centre, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom
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  • Ian P. Crocker

    Corresponding author
    1. Maternal and Fetal Health Research Centre, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom
    • Maternal and Fetal Health Research Centre, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Research Floor, St Mary's Hospital, Oxford Road, Manchester, M13 9WL, United Kingdom
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    • Telephone: +44(0)161-701-6973; Fax: +44(0)161-701-6971


  • Author contributions: P.S.: conception and design, collection and assembly of data, data analysis and interpretation, and manuscript writing.; W.R., S.B., and H.S.: collection of data; X.F.: provision of study material; M.W., C.A.H., P.N.B., and C.P.S.: financial support and final approval of manuscript; C.H.: provision of study material, financial support, and final approval of manuscript; S.T.D.: final approval of manuscript; I.P.C.: financial support, design, data analysis and interpretation, manuscript writing, and final approval of manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    first published online in STEM CELLS EXPRESS April 4, 2013.

Abstract

The potency of adult-derived circulating progenitor endothelial colony forming cells (ECFCs) is drastically surpassed by their fetal counterparts. Human pregnancy is associated with robust intensification of blood flow and vascular expansion in the uterus, crucial for placental perfusion and fetal supply. Here, we investigate whether fetal ECFCs transmigrate to maternal bloodstream and home to locations of maternal vasculogenesis, primarily the pregnant uterus. In the first instance, endothelial-like cells, originating from mouse fetuses expressing paternal eGFP, were identified within uterine endothelia. Subsequently, LacZ or enhanced green fluorescent protein (eGFP)-labeled human fetal ECFCs, transplanted into immunodeficient (NOD/SCID) fetuses on D15.5 pregnancy, showed similar integration into the mouse uterus by term. Mature endothelial controls (human umbilical vein endothelial cells), similarly introduced, were unequivocally absent. In humans, SRY was detected in 6 of 12 myometrial microvessels obtained from women delivering male babies. The copy number was calculated at 175 [IQR 149–471] fetal cells per millimeter square endothelium, constituting 12.5% of maternal vessel lumina. Cross-sections of similar human vessels, hybridized for Y-chromosome, positively identified endothelial-associated fetal cells. It appears that through ECFC donation, fetuses assist maternal uterine vascular expansion in pregnancy, potentiating placental perfusion and consequently their own fetal supply. In addition to fetal growth, this cellular mechanism holds implications for materno-fetal immune interactions and long-term maternal vascular health. STEM Cells2013;31:1363–1370

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