Role of Placental VDR Expression and Function in Common Late Pregnancy Disorders

Abstract

Vitamin D, besides its classical role in bone metabolism, plays a distinct role in multiple pathways of the feto-maternal unit. Calcitriol is the major active ligand of the nuclear vitamin D receptor (VDR). The vitamin D receptor (VDR) is expressed in different uteroplacental parts and exerts a variety of functions in physiologic pregnancy. It regulates decidualisation and implantation, influences hormone secretion and placental immune modulations. This review highlights the role of the vitamin D receptor in physiologic and disturbed pregnancy, as preeclampsia, fetal growth restriction, gestational diabetes and preterm birth. We discuss the existing literature regarding common VDR polymorphisms in these pregnancy disorders.

Keywords: GDM; VDR; fetal growth restriction; preeclampsia; preterm birth; vitamin D.

Figure 1

Vitamin D receptor expression and polymorphism: Vitamin D receptor (VDR) is a part of the nuclear steroid family and is also expressed in the plasma membrane. The major active ligand of VDR is 1α,25-(OH)₂D (calcitriol). In nucleus, VDR recruits retinoid X receptor (RXR) to form a heterodimer, which binds to vitamin D response element (VDRE) and modulates the transcription of numerous genes. VDR gene is located on the chromosome 12q12-14, which consists of eight protein exons (namely, 2–9) and six untranslated exons (1A–1F). VDR has four well-characterized di-allelic polymorphisms: BsmI and ApaI on the last intron, FokI and TaqI on the coding sequence. Among these polymorphisms ApaI, FokI and TaqI are linked to gestational diabetes mellitus (GDM), ApaI and FokI are linked to preterm birth.