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Placental vitamin D receptor expression is decreased in human idiopathic fetal growth restriction

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Abstract

Fetal growth restriction (FGR) affects up to 5 % of pregnancies worldwide, and trophoblast function plays a significant role on the outcome. An epidemiological study has linked vitamin D deficiency to adverse perinatal outcomes, which include decreased birth weight. The placenta as an important source of vitamin D regulates its metabolism through the vitamin D receptor (VDR), but the mechanism by which VDR regulates trophoblast function is poorly understood. Our study aimed at determining placental VDR expression in FGR and gestation-matched control (GMC) pregnancies and identifying the actions of VDR in trophoblast differentiation and apoptosis. Placentae were collected from a well-defined cohort of idiopathic FGR and GMC pregnancies. VDR mRNA and protein expressions were determined by PCR, immunohistochemistry and immunoblotting, while functional consequences of VDR inactivation in vitro were determined on BeWo cells by determining changes in differentiation, attachment and apoptosis. Significant decreases in VDR mRNA expression (p = 0.0005) and protein expression (p = 0.0003) were observed in the FGR samples, while VDR inactivation, which showed markers for differentiation, cell attachment and apoptosis, was significantly increased. Thus, decreased placental VDR may contribute to uncontrolled premature differentiation and apoptosis of trophoblasts that are characteristics of idiopathic FGR pregnancies.

Key message

  • Fetal growth restriction (FGR) affects up to 5 % of all pregnancies worldwide.

  • FGR is the second highest cause of perinatal mortality and morbidity.

  • The placenta plays a pivotal role in vitamin D metabolism during pregnancy.

  • Vitamin D deficiency is associated with adverse pregnancy outcomes.

  • Placental vitamin D receptor expression is decreased in FGR.

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Author contributions

T.P.H.N. contributed by performing the laboratory work, acquisition of data, analysis and interpretation, drafting and revision of the manuscript.

H.E.J.Y. assisted with the data analysis and interpretation, and revision of the manuscript.

T.C. contributed by assisting with the optimisation of cell culture experiments, data analysis and revision of the manuscript.

A.J.B. assisted with the real-time PCR analyses, data acquisition and revision of the manuscript.

S.P.B. contributed to the clinical characterisation of patient samples and critical revision of the manuscript for its intellectual content.

P.M. contributed substantially to the study concept and experimental design, data acquisition, analysis and interpretation and critical revision of the manuscript for its intellectual content.

Conflict of interest

The authors have nothing to disclose.

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  1. P. Murthi

    Present address: North West Academic Centre, University of Melbourne, St Albans, Victoria, 3021, Australia

Authors and Affiliations

  1. Department of Perinatal Medicine Pregnancy Research Centre, The University of Melbourne, Melbourne, Australia

    T. P. H. Nguyen, H. E. J. Yong, T. Chollangi, A. J. Borg, S. P. Brennecke & P. Murthi

  2. Department of Obstetrics and Gynaecology, The Royal Women’s Hospital, Parkville, Victoria, 3052, Australia

    T. P. H. Nguyen, H. E. J. Yong, T. Chollangi, A. J. Borg, S. P. Brennecke & P. Murthi

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  1. T. P. H. Nguyen
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Nguyen, T.P.H., Yong, H.E.J., Chollangi, T. et al. Placental vitamin D receptor expression is decreased in human idiopathic fetal growth restriction. J Mol Med 93, 795–805 (2015). https://doi.org/10.1007/s00109-015-1267-1

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