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Vitamin D promotes human extravillous trophoblast invasion in vitro.
Chan, S Y; Susarla, R; Canovas, D; Vasilopoulou, E; Ohizua, O; McCabe, C J; Hewison, M; Kilby, M D.
Afiliación
  • Chan SY; Centre for Women's & Children's Health and the School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
  • Susarla R; Centre for Women's & Children's Health and the School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
  • Canovas D; Centre for Women's & Children's Health and the School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
  • Vasilopoulou E; Centre for Women's & Children's Health and the School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
  • Ohizua O; Women, Children and Sexual Health Directorate, Walsall Hospitals NHS Trust, Walsall, WS2 9PS, UK.
  • McCabe CJ; Centre for Endocrinology, Diabetes and Metabolism, and the School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, The University of Birmingham, Birmingham, B15 2TT, UK.
  • Hewison M; Centre for Endocrinology, Diabetes and Metabolism, and the School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, The University of Birmingham, Birmingham, B15 2TT, UK.
  • Kilby MD; Centre for Women's & Children's Health and the School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK; Fetal Medicine Centre, Birmingham Women's NHS Foundation Trust, Edgbaston, Birmingham, B15 2TG, UK. E
Placenta ; 36(4): 403-9, 2015 Apr.
Article en En | MEDLINE | ID: mdl-25596923
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Placentación / Trofoblastos / Calcifediol / Calcitriol / Regulación hacia Arriba / Catelicidinas / Vitamina D3 24-Hidroxilasa Límite: Female / Humans / Pregnancy Idioma: En Revista: Placenta Año: 2015 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Placentación / Trofoblastos / Calcifediol / Calcitriol / Regulación hacia Arriba / Catelicidinas / Vitamina D3 24-Hidroxilasa Límite: Female / Humans / Pregnancy Idioma: En Revista: Placenta Año: 2015 Tipo del documento: Article Pais de publicación: Países Bajos