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Vitamin D and Placental-Decidual Function

Judith N. Bulmer, PhD

Mark D. Kilby, MD

Division of Medical Sciences, Institute of Biomedical Research, The University of Birmingham, Queen Elizabeth Hospital, Birmingham; Department of Pathology, Royal Victoria Infirmary, Queen Victoria Road, Newcastle-upon-Tyne; Department of Fetal Medicine, Birmingham Women's Hospital, Birmingham, United Kingdom

Martin Hewison, PhD

Division of Medical Sciences, Institute of Biomedical Research, The University of Birmingham, Queen Elizabeth Hospital, Birmingham; Department of Pathology, Royal Victoria Infirmary, Queen Victoria Road, Newcastle-upon-Tyne; Department of Fetal Medicine, Birmingham Women's Hospital, Birmingham, United Kingdom; M.Hewison{at}bham.ac.uk

The active form of vitamin D (1,25-dihydroxyvitamin D₃, 1,25[OH]₂D₃) has well-established effects on bone metabolism and mineral homeostasis. However, recently it has become clear that 1,25(OH)₂D₃ has potent antiproliferative and immunomodulatory actions that are not immediately linked to its role as a skeletal regulator. Both the nuclear receptor for 1,25(OH)₂D₃ (vitamin D receptor, VDR) and the vitamin D-activating enzyme 1-hydroxylase are expressed in a wide variety of nonclassic tissues, highlighting the potential for local autocrine-paracrine responses rather than traditional endocrine effects. Prominent among the tissues that express 1-hydroxylase is the placenta-decidua, and this has raised important questions concerning the potential role of locally generated 1,25(OH)₂D₃ as a modulator of fetal-placental development and function. When bound to the VDR, 1,25(OH)₂D₃ regulates key target genes associated with implantation, such as HOXA10, whereas the potent immunosuppressive effects of 1,25(OH)₂D₃ suggest a role in implantation tolerance. These observations are further supported by data from our group showing increased expression of 1hydroxylase and VDR in first-trimester trophoblast and decidua from human pregnancies. Studies by other groups have reported abnormal expression of 1-hydroxylase in preeclamptic pregnancies, revealing a poential role for 1,25(OH)₂D₃ as a regulator of placentation. The effect of vitamin D on reproduction has been further endorsed by murine gene knockout models for 1-hydroxylase and VDR, both of which are infertile. These observations and other are discussed in this article in which we postulate an active role for 1,25(OH)₂D₃ in placenta-decidua. In particular, we describe how induction of the vitamin D—activating enzyme 1-hydroxylase in early gestation might provide a mechanism by which environmental or dietary vitamin D can influence fetal-placental development.

Key Words: Vitamin D • 1-hydroxylase • placenta • decidua • implantation

Journal of the Society for Gynecologic Investigation, Vol. 11, No. 5, 263-271 (2004)
DOI: 10.1016/j.jsgi.2004.02.002


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