PM.02 Effect of 1, 25-Dihydroxyvitamin D3 (1, 25-D3) on Extravillious Trophoblast Invasion in Vitro. (26th April 2013)

• Record Type: Journal Article
• Authors: Chan, SY; Cavonas, D; Vasilopoulou, E; Loubiere, LS; Ohizua, O; Hewison, M; Kilby, MD
• Is Part Of: Archives of disease in childhood. Volume 98(2013)Supplement 1
• Page Start: A26
• Page End: A26
• Publication Date: 2013-04-26
• Subjects: Infants -- Diseases -- Periodicals; Newborn infants -- Diseases -- Periodicals; Fetus -- Diseases -- Periodicals; 618.920105
• DOI: 10.1136/archdischild-2013-303966.087
• Languages: English
• ISSNs: 1359-2998

Abstract

Abstract : Introduction: The invasion of maternal tissues by extravillous trophoblast (EVT) plays a central role in normal placentation. Inadequate EVT invasion is characteristic of pre-eclampsia, which is associated with low maternal circulatory concentrations of 25-hydroxyvitamin D3 (25-D3 ). Furthermore, trophoblasts from pre-eclamptic placentae demonstrate lower 1α-hydroxylase activity, which converts 25-D3 to the active ligand, 1.25-D3 . We thus hypothesise that reduced vitamin D action leads to malplacentation and increase pre-eclampsia risk. To elucidate the mechanistic link we determined whether 1.25-D3 has a regulatory effect on EVT invasion. Methods: Primary EVT cells were isolated from first trimester (9–11 weeks) human placentae (n = 5) following surgical termination of pregnancy. Isolated EVT, and in separate experiments, SGHPL4 (EVT-like cell line) were placed in 8-µm inserts coated with reduced growth factor Matrigel® and treated with increasing concentrations of 1.25-D3 (0.0.1.1.10 nM). EVT invasion was quantified by counting all the invaded cells visualised with Mayer's haematoxylin and eosin at 48 hours. A proliferative response to 1.25-D3 was assessed by MTT assays. Results: 1, 25-D3 promoted EVT invasion in a dose-dependent manner peaking at a dose of 1 nM. EVT exposed to 0.1 nM and 1 nM concentrations showed a 1.9-fold (p < 0.05) and 2-fold (p < 0.01) increase respectively in the numbers of invaded cells compared with untreated controls. Treatment with 10 nM 1.25-D3 induced a 10-fold (p < 0.05) increase in invasion by SGHPL-4 cells compared with 0 nM but did not affect proliferation. Conclusion: This is circumstantial evidence that Vitamin D supplementation during pregnancy may potentially reduce the risk of developing pre-eclampsia as 1.25-D3 promotes EVT invasion.