Vitamin D, the placenta and early pregnancy: effects on trophoblast function

    1. Martin Hewison1,3
    1. 1Institute of Metabolism and Systems Research, The University of Birmingham, Birmingham, UK
    2. 2Fetal Medicine Centre, Birmingham Women’s NHS Foundation Trust, Birmingham, UK
    3. 3CEDAM, Birmingham Health Partners, The University of Birmingham, Birmingham, UK
    4. 4Division of Developmental Biology and Medicine, Maternal and Fetal Health Research Centre, School of Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
    5. 5Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
    6. 6School of Life and Health Sciences, Aston University, Birmingham, UK
    1. Correspondence should be addressed to M Hewison: m.hewison{at}


    Pregnancy is associated with significant changes in vitamin D metabolism, notably increased maternal serum levels of active vitamin D, 1,25-dihydroxyvitamin (1,25(OH)2D). This appears to be due primarily to increased renal activity of the enzyme 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1) that catalyzes synthesis of 1,25(OH)2D, but CYP27B1 expression is also prominent in both the maternal decidua and fetal trophoblast components of the placenta. The precise function of placental synthesis of 1,25(OH)2D remains unclear, but is likely to involve localized tissue-specific responses with both decidua and trophoblast also expressing the vitamin D receptor (VDR) for 1,25(OH)2D. We have previously described immunomodulatory responses to 1,25(OH)2D by diverse populations of VDR-expressing cells within the decidua. The aim of the current review is to detail the role of vitamin D in pregnancy from a trophoblast perspective, with particular emphasis on the potential role of 1,25(OH)2D as a regulator of trophoblast invasion in early pregnancy. Vitamin D deficiency is common in pregnant women, and a wide range of studies have linked low vitamin D status to adverse events in pregnancy. To date, most of these studies have focused on adverse events later in pregnancy, but the current review will explore the potential impact of vitamin D on early pregnancy, and how this may influence implantation and miscarriage.

    • Received 24 October 2017
    • Accepted 6 November 2017
    • Made available online as an Accepted Preprint 6 November 2017
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