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PM.02 Effect of 1,25-Dihydroxyvitamin D3 (1,25-D3) on Extravillious Trophoblast Invasion in Vitro
  1. SY Chan1,
  2. D Cavonas1,
  3. E Vasilopoulou1,
  4. LS Loubiere1,
  5. O Ohizua2,
  6. M Hewison3,
  7. MD Kilby1
  1. 1University of Birmingham, Birmingham, UK
  2. 2Walsall Hospitals NHS Trust, Walsall, UK
  3. 3UCLA Orthopaedic Hospital, Los Angeles, United States of America


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 ( 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.

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