Vitamin D effects on pregnancy and the placenta

Abstract

Vitamin D is a pleiotropic secosteroid hormone important for health and disease prevention. The actions of vitamin D are mediated by the vitamin D receptor that binds the active form of vitamin D [1,25(OH)(2)D] to induce both transcriptional and non-genomic responses. Vitamin D has well known classical functions in calcium uptake and bone metabolism, but more recent work highlights the importance of the nonclassical actions of vitamin D in a variety of cell types. These actions include modulation of the innate and adaptive immune systems and regulation of cell proliferation. Adequate vitamin D intake is essential for maternal and fetal health during pregnancy, and epidemiological data indicate that many pregnant women have sub-optimal vitamin D levels. Notably, vitamin D deficiency correlates with preeclampsia, gestational diabetes mellitus, and bacterial vaginosis, and an increased risk for C-section delivery. Recent work emphasizes the importance of nonclassical roles of vitamin D in pregnancy and the placenta. The placenta produces and responds to vitamin D where vitamin D functions as a modulator of implantation, cytokine production and the immune response to infection. We describe vitamin D metabolism and the cellular responses to vitamin D, and then summarize the role of vitamin D in placental trophoblast, pregnancy and the fetus.

Copyright © 2010 Elsevier Ltd. All rights reserved.

Figures

Figure 1

Chemical structures of vitamins D2 and D3.

Figure 2. Synthesis and metabolism of vitamin D

Vitamin D2 and D3 can be obtained by diet. Vitamin D2 is metabolized similarly to vitamin D3, but with only one third of the biological activity (see text). Vitamin D3 is synthesized photochemically in the skin from 7-dehydrocholesterol by ultraviolet B exposure and converted to 25OHD3 by a 25-hydroxylase in the liver. The major circulating form of vitamin D, 25OHD3, is hydroxylated in the kidney, placenta, and other tissues by the enzyme, 1α– hydroxylase (encoded by the CYP27B1 gene), to the bioactive form, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. The enzyme, 24-hydroxylase (encoded by the CYP24A1 gene), catabolizes both 25OHD3 and 1,25(OH)2D3 to inactive metabolites 24,25(OH)2D3 and 1,24,25(OH)3D3, respectively, which are then excreted.

Figure 3

Genomic and non-genomic responses of vitamin D receptor binding to 1,25(OH)2D. In the genomic response, 1,25(OH)2D binds to the nuclear vitamin D receptor (VDR). Heterodimerization of the VDR with the retinoid X receptor (RXR) and binding to vitamin D response elements (VDREs) in the promoters of target genes affects transcription, usually by increasing transcription, and generating downstream biological responses. In the non-genomic response pathway, binding of 1,25(OH)2D to VDR associated with caveolae of the plasma membrane activates one or more second messenger systems to elicit rapid responses. PI3K, phosphatidylinositol-3-kinase; PKC, protein kinase C