Evidence for Extra-Renal 1 α-Hydroxylation of 25-Hydroxyvitamin D
            <sub>3</sub>
            in Pregnancy

Gray, T K; Lester, Gayle E.; Rs, Lorenc

doi:10.1126/science.451538

Cited by 201 publications

(96 citation statements)

References 15 publications

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“…More than 30 y ago, the placenta was identified as a major site for conversion of 25OHD to the active form of vitamin D, 1,25-dihydroxyvitamin D 3 (1,25[OH] 2 D 3 ), with both maternal decidua and fetal trophoblast demonstrating activity of the enzyme 1a-hydroxylase (CYP27B1) (7,8). However, since then, the precise function of this extrarenal CYP27B1 has remained unclear.…”

mentioning

confidence: 99%

Vitamin D and the Regulation of Placental Inflammation

Liu

Kaplan

Lagishetty

et al. 2011

The Journal of Immunology

182

118

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The vitamin D-activating enzyme 1α-hydroxylase (CYP27B1) and vitamin D receptor (VDR) support anti-inflammatory responses to vitamin D in many tissues. Given the high basal expression of CYP27B1 and VDR in trophoblastic cells from the placenta, we hypothesized that anti-inflammatory effects of vitamin D may be particularly important in this organ. Pregnant wild type (WT) mice i.p. injected with LPS showed elevated expression of mouse Cyp27b1 (4-fold) and VDR (6-fold). Similar results were also obtained after ex vivo treatment of WT placentas with LPS. To assess the functional impact of this, we carried out ex vivo studies using placentas −/− for fetal (trophoblastic) Cyp27b1 or VDR. Vehicle-treated −/− placentas showed increased expression of IFN-γ and decreased expression of IL-10 relative to +/+ placentas. LPS-treated −/− placentas showed increased expression of TLR2, IFN-γ, and IL-6. Array analyses identified other inflammatory factors that are dysregulated in Cyp27b1−/− versus Cyp27b1+/+ placentas after LPS challenge. Data highlighted enhanced expression of IL-4, IL-15, and IL-18, as well as several chemokines and their receptors, in Cyp27b1−/− placentas. Similar results for IL-6 expression were observed with placentas −/− for trophoblastic VDR. Finally, ex vivo treatment of WT placentas with the substrate for Cyp27b1, 25-hydroxyvitamin D3, suppressed LPS-induced expression of IL-6 and the chemokine Ccl11. These data indicate that fetal (trophoblastic) vitamin D plays a pivotal role in controlling placental inflammation. In humans, this may be a key factor in placental responses to infection and associated adverse outcomes of pregnancy.

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mentioning

confidence: 99%

Vitamin D and the Regulation of Placental Inflammation

Liu

Kaplan

Lagishetty

et al. 2011

The Journal of Immunology

182

118

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“…4). Following the reports of Weisman et al [5], Gray et al [6], and Tanaka et al [7], kidney is no longer considered to be the sole site of 25-(OH)D,-1 a-hydroxylation during pregnancy. Several studies have reported that the term human feto-placental unit can produce 1,25-(OH),D, [8-131.…”

Section: Resultsmentioning

confidence: 99%

“…This concept is based on experimental results showing that 1,25-(OH)*D3 is no longer formed after bilateral nephrectomy [l]. However, this is clearly not the case during pregnancy, as rat maternal blood contains 1,25-(OH),D, even after experimental bilateral nephrectomy [5,6], and as foeto-placental tissues from both animals and humans synthesize 1,25-(OH),D, in vitro [7-131. Studies on the ability of the human uterine cells to synthesize 1,25-(OH),D, have so far been mostly limited to the late pregnancy period [g-13], and/or have involved incubations with whole tissue homogenates [8,9,12,13]. The location and characterization of the cells responsible for the 1,25-(OH),D, synthesis in the feto-placental unit at this time of pregnancy remains a fertile field for debate [8-131.…”

Section: Introductionmentioning

confidence: 99%

Uterine cells other than stromal decidual cells are required for 1,25‐dihydroxyvitamin D₃ production during early human pregnancy

Kachkache¹,

Rebut-Bonneton²,

Cynober³

et al. 1993

FEBS Letters

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Human decidual cells are known to produce l,25-(OH)2Dg at the end of pregnancy, the present study evaluates this capacity, and the part played by stromal decidual cells, in early pregnancy. Cells were obtained from nine human decidua by aspiration or curettage during early pregnancy (7-10 weeks), separated on Ficoll-Paque and plastic adherence, and incubated for 1 h with 25-(OH)D1. Incubation medium and cells were extracted and chromatographed on two successive HPLC systems. The cells examined were of both physiological and pathological (ectopic pregnancy) origin. Endometrial cells obtained in four non-pregnant situations (myomas) were also studied to determine whether the l,25-(OH)zD, synthesis by the uterus is associated with the appearance of decidual cells. Results show that human decidual cells from early pregnancy convert 25(OH)D, (2.5 nM or 2.5 PM) into a metabolite with the physicochemical characteristics of synthetic 1,25-(OH),D,. This ability is shared by cells isolated during early pregnancy, whether physiological or ectopic (tubal pregnancy). Non-adherent cells, which include mainly stromal decidual cells, are less able to produce 1,25-(OH),D, than are the adherent cells, suggesting that macrophages, granulocytes or as yet unidentified cell types are required for the l,25-(OH)2D, production by decidual tissue during early human pregnancy. In addition, one out of four experiments with non-pregnant endometrial cells could produce 1,25-(OH),D, suggesting that, although not the rule in the non-pregnant state, in vitro production of l,25-(OH)2Dg by uterine cells can be found in the absence of decidual cells.

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“…Historically, the placenta was one of the first of these extra-renal tissues shown to be capable of synthesizing 1,25(OH) 2 D, with CYP27B1 activity being detectable in both maternal decidua and fetal trophoblast. 26,27 Since then we have characterized the spatio-temporal organization of placental CYP27B1 and VDR across gestation, confirming that the enzyme and receptor are localized to both the maternal decidua and fetal trophoblast. Significantly, both proteins are more abundant in 1 st and 2 nd trimester tissue.…”

Section: Vitamin D and Human Pregnancy 69mentioning

confidence: 95%

Vitamin D and Human Pregnancy

Grayson¹,

Hewison

2011

Fet. Matern. Med. Rev.

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At the end of 2007, Time magazine listed the “benefits of vitamin D” as one of its top 10 medical breakthroughs for that year. Since then there has been a remarkable upsurge of interest in vitamin D, with new research advances seemingly published on a weekly basis. In particular, there has been increasing awareness of the variability of vitamin D status in populations across the globe and, significantly, a growing debate about the need for revised parameters for vitamin D supplementation. Although sub-optimal vitamin D is likely to be a widespread problem for 21stcentury societies, it is also clear that some groups are at much greater risk of low vitamin D status. Prominent amongst these are pregnant women and the aim of the following review article will be to discuss this problem in further detail with specific emphasis on its potential physiological and clinical impact.

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Evidence for Extra-Renal 1 α-Hydroxylation of 25-Hydroxyvitamin D ₃ in Pregnancy

Cited by 201 publications

References 15 publications

Vitamin D and the Regulation of Placental Inflammation

Vitamin D and the Regulation of Placental Inflammation

Uterine cells other than stromal decidual cells are required for 1,25‐dihydroxyvitamin D₃ production during early human pregnancy

Vitamin D and Human Pregnancy

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Evidence for Extra-Renal 1 α-Hydroxylation of 25-Hydroxyvitamin D 3 in Pregnancy

Cited by 201 publications

References 15 publications

Vitamin D and the Regulation of Placental Inflammation

Vitamin D and the Regulation of Placental Inflammation

Uterine cells other than stromal decidual cells are required for 1,25‐dihydroxyvitamin D3 production during early human pregnancy

Vitamin D and Human Pregnancy

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About

Evidence for Extra-Renal 1 α-Hydroxylation of 25-Hydroxyvitamin D ₃ in Pregnancy

Uterine cells other than stromal decidual cells are required for 1,25‐dihydroxyvitamin D₃ production during early human pregnancy