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Vitamin D promotes human extravillous trophoblast invasion in vitro

Chan, SY, Chan, R, Canovas, D, Vasilopoulou, Elisavet, Ohizua, O, McCabe, CJ, Hewison, M, Kilby, MD (2015) Vitamin D promotes human extravillous trophoblast invasion in vitro. Placenta, 36 (4). pp. 403-409. ISSN 0143-4004. (doi:10.1016/j.placenta.2014.12.021)

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Abstract

Introduction 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. Methods This study assessed the effects of the active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25-D3), and its precursor, 25-hydroxyvitamin D3 (25-D3), 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-D3 receptor (VDR) was assessed by immunocytochemistry. EVT responses following in vitro treatment with 1,25-D3 (0–10 nM) or 25-D3 (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® were quantified alongside zymographic analysis of secreted matrix metalloproteinases (MMPs). Effects on cell viability were assessed by measurement of MTT. Results 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-D3 treatment. EVT could respond to 1,25-D3 and 25-D3, both of which significantly increased EVT invasion, with maximal effect at 1 nM 1,25-D3 (1.9-fold; p < 0.01) and 100 nM 25-D3 (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. Discussion 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.

Item Type: Article
DOI/Identification number: 10.1016/j.placenta.2014.12.021
Uncontrolled keywords: Vitamin D; Pre-eclampsia; Placenta; Extravillous trophoblast; Cell invasion
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: E. Vasilopoulou
Date Deposited: 18 Sep 2017 10:39 UTC
Last Modified: 29 May 2019 19:32 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/63461 (The current URI for this page, for reference purposes)
Vasilopoulou, Elisavet: https://orcid.org/0000-0002-1940-0333
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