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.
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