Vitamin D promotes human extravillous trophoblast invasion in vitro. Issue 4 (April 2015)

• Record Type: Journal Article
• Authors: Chan, S.Y.; Susarla, R.; Canovas, D.; Vasilopoulou, E.; Ohizua, O.; McCabe, C.J.; Hewison, M.; Kilby, M.D.
• Is Part Of: Placenta. Volume 36:Issue 4(2015:Apr.)
• Page Start: 403
• Page End: 409
• Publication Date: 2015-04
• Subjects: Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2014.12.021
• Languages: English
• ISSNs: 0143-4004

Abstract

<abstract xml:lang="en" abstract-type="author" id="abs0010"> <title id="sectitle0010">Abstract</title> <sec> <title id="sectitle0015">Introduction</title> <p id="abspara0010">Incomplete human extravillous trophoblast (EVT) invasion of the decidua and maternal spiral arteries is characteristic of pre-eclampsia, a condition linked to low maternal vitamin D status. It is hypothesized that dysregulated vitamin D action in uteroplacental tissues disrupts EVT invasion leading to malplacentation.</p> </sec> <sec> <title id="sectitle0020">Methods</title> <p id="abspara0015">This study assessed the effects of the active vitamin D metabolite, 1, 25-dihydroxyvitamin D<sub>3</sub> (1, 25-D<sub>3</sub>), and its precursor, 25-hydroxyvitamin D<sub>3</sub> (25-D<sub>3</sub>), on primary human EVT isolated from first trimester pregnancies. Expression of EVT markers (cytokeratin-7, HLA-G), the vitamin D-activating enzyme (CYP27B1) and 1, 25-D<sub>3</sub> receptor (VDR) was assessed by immunocytochemistry. EVT responses following <italic>in vitro</italic> treatment with 1, 25-D<sub>3</sub> (0–10 nM) or 25-D<sub>3</sub> (0–100 nM) for 48–60 h were assessed using quantitative RT-PCR (qRT-PCR) analysis of key target genes. Effects on EVT invasion through Matrigel<sup>®</sup> were quantified alongside zymographic analysis of secreted matrix metalloproteinases (MMPs). Effects on cell viability were assessed by measurement of MTT.</p> </sec> <sec> <title id="sectitle0025">Results</title> <p id="abspara0020">EVT co-expressed mRNA and protein for CYP27B1 and VDR, and demonstrated induction of mRNA encoding vitamin D-responsive genes, 24-hydroxylase (CYP24A1) and cathelicidin following 1, 25-D<sub>3</sub> treatment. EVT could respond to 1, 25-D<sub>3</sub> and 25-D<sub>3</sub>, both of which significantly increased EVT invasion, with maximal effect at 1 nM 1, 25-D<sub>3</sub> (1.9-fold; p < 0.01) and 100 nM 25-D<sub>3</sub> (2.2-fold; p < 0.05) respectively compared with untreated controls. This was accompanied by increased pro-MMP2 and pro-MMP9 secretion. The invasion was independent of cell viability, which remained unchanged.</p> </sec> <sec> <title id="sectitle0030">Discussion</title> <p id="abspara0025">These data support a role for vitamin D in EVT invasion during human placentation and suggest that vitamin D-deficiency may contribute to impaired EVT invasion and pre-eclampsia.</p> </sec> </abstract>