Possible roles for folic acid in the regulation of trophoblast invasion and placental development in normal early human pregnancy

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Williams, Paula J., Bulmer, Judith N., Innes, Barbara A. and Broughton Pipkin, Fiona (2011) Possible roles for folic acid in the regulation of trophoblast invasion and placental development in normal early human pregnancy. Biology of Reproduction, 84 (6). pp. 1148-1153. ISSN 1529-7268

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Abstract

In addition to its role in the prevention of neural tube defects, folic acid has many other physiological functions, including cell proliferation, DNA replication, and antioxidant protection. The aim of this study was to determine the role that folic acid has in regulating placental trophoblast development. Placental explants from placentae at gestational age 7 wk (n ¼ 3) were cultured in folic acid at concentrations of 106 M, 108 M, and 1010 M. Extravillous trophoblast (EVT) invasion was assessed

following 6-day culture, and explants were used for immunohistochemical evaluation of proliferation (MKI67) and apoptosis (active caspase 3). In addition, an array was performed on cell culture supernatants to examine a range of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs). Folic acid increased the invasion of EVT cells in this explant model by between 83% and 19% (P ¼ 0.005), and this was associated with increased MKI67 positivity and decreased active caspase 3 positivity; this effect was concentration dependent and showed a biphasic response. In addition, culture in folic acid increased vascular density, as determined by anti-CD31 immunostaining

(P ¼ 0.05). The increase in EVT invasion correlated with increased placental explant secretion of MMP2 (P ¼ 0.01),

MMP3 (P¼0.01), and MMP9 (P¼0.02). This study demonstrates

that folic acid is potentially important in a number of crucial early stages of placental development, including EVT invasion, angiogenesis, and secretion of MMPs, and highlights the need for further studies to address the benefit of longer-term folic acid supplementation throughout pregnancy to prevent pregnancy disorders associated with deficient placental development, including preeclampsia.

Item Type: Article
RIS ID: https://nottingham-repository.worktribe.com/output/707462
Keywords: Folic acid, Placenta, Pregnancy, Trophoblast
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Life Sciences > School of Molecular Medical Sciences
Identification Number: 10.1095/biolreprod.110.088351
Depositing User: Chamberlain, Mr Dick
Date Deposited: 22 Apr 2014 12:40
Last Modified: 04 May 2020 16:30
URI: https://eprints.nottingham.ac.uk/id/eprint/2617

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