Spontaneous Miscarriage strongly associated with 2 vitamin D genes

Created February 2020

Altered decidual and placental catabolism of vitamin D may contribute to the aetiology of spontaneous miscarriage

Placenta, Volume 92, March 2020, Pages 1-8, https://doi.org/10.1016/j.placenta.2020.01.013

lH.HouaJ.Y.ZhangaD.ChenaF.DengbA.N.MorsebX.QiucP.HebG.E.Lasha

1. Items in both categories Pregnancy and Vitamin D Receptor:{category} 1. Items in both categories Pregnancy and Vitamin D Binding Protein:{category} 1. Items in both categories Pregnancy and other Vitamin D Genes:{category} 1. Miscarriage in 29 Vitamin D Life titles as of Dec 2021

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Placenta

Decidua

Highlights

Placental/decidual levels of vitamin D are decreased in spontaneous miscarriage.
CYP enzyme expression changes may be linked to hyperoxia.
VDR expression changes may be linked to infection.

Introduction

Vitamin D catabolizing enzymes, along with vitamin D receptor (VDR) and vitamin D binding protein (DBP) are expressed in the decidua and placenta during pregnancy and capable of synthesizing active vitamin D. Vitamin D plays roles in immunoregulation and trophoblast invasion, key features of a successful pregnancy. Epidemiological data suggests that vitamin D deficiency is associated with both spontaneous and recurrent miscarriage but few studies have investigated the expression of the key vitamin D catabolizing enzymes in miscarriage.

Methods

Placenta and decidua were collected after termination of apparently normal pregnancies (controls, n = 22) or spontaneous miscarriage (n = 20). Immunohistochemical staining, Western Blot and qRT-PCR were performed for CYP27B1, CYP24A1, CYP2R1, VDR and DBP (not qRT-PCR). HTR-8/SVneo cells were cultured in CoCL2 (hypoxic mimetic) or LPS (bacterial infection mimetic) for 24 h, RNA extracted and qRT-PCR performed for CYP27B1, CYP24A1, CYP2R1 and VDR.

Results

In spontaneous miscarriage, placental and decidual

expression of CYP27B1 was reduced, while
expression of CYP24A1, VDR and DBP was increased.

When a trophoblast cell line was treated with CoCL2 expression of CYP27B1 was increased and CYP24A1 was reduced, while LPS induced expression of VDR.

Discussion

This is the first report of altered utero-placental vitamin D catabolism in spontaneous miscarriage. It is becoming accepted that women who are undergoing assisted reproductive technologies should ensure they have sufficient vitamin D levels prior to pregnancy, these data support that all women should ensure they are vitamin D replete before planning to get pregnant.