The Liver X Receptor in Correlation with Other Nuclear Receptors in Spontaneous and Recurrent Abortions

Julia Knabl,Lena Welbergen,Stefan Hutter,Regina Ensenauer,Aurelia Pestka,Maria Günthner-Biller,Rebecca Hüttenbrenner,Udo Jeschke,Torsten Plösch

doi:10.1155/2013/575604

Julia Knabl, Lena Welbergen + Show 7 more

Open Access

https://doi.org/10.1155/2013/575604

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Abstract

The liver X receptors (LXRs) have been shown to be crucially involved in maternal-fetal cholesterol transport and placentation. The aim of this study was to investigate the expression pattern and frequency of LXR under normal physiological circumstances and in spontaneous abortion and/or recurrent miscarriage. A total of 29 (12 physiologic pregnancies/10 spontaneous abortions/7 recurrent miscarriages) human pregnancies in first trimester were analysed for LXR expression. Expression changes were evaluated by immunohistochemistry for receptor and quantitative RT-PCR (TaqMan) was performed to determine the level of LXR mRNA expression. We also stained for RXRα and PPARγ as possible heterodimers of LXR. LXR expression was downregulated in the syncytiotrophoblast of spontaneous abortion placentas compared to normal pregnancy. In recurrent miscarriage there was a trend for a downregulation. Decidua showed an even stronger downregulation in both groups. In the syncytiotrophoblast we found a positive correlation for the combination of LXR/PPARγ in abortions and a negative correlation for LXR/RXRα. In addition, double-immunofluorescence staining showed that LXR as well as RXRα and PPARγ are expressed by the extravillous trophoblast. Finally, RXRα and LXR showed coexpression in the same extravillous trophoblast cells. To conclude, our data show that LXR expression is decreased in miscarriage.

Highlights

Multiple regulatory mechanisms are involved in the success of human pregnancy and disturbances in any of these processes can lead to fetal loss
We identified the expression of liver X receptors (LXRs) in nuclei of cells in the decidua and the syncytiotrophoblast both in regular pregnancy and miscarriage (Figure 1)
LXR expression was significantly reduced in the syncytiotrophoblast of spontaneous abortion compared to normal pregnancy (IRS 8 versus 3, P = 0.007) (Figure 1(a))

Summary

Introduction

Multiple regulatory mechanisms (e.g., immunologic, endocrine, and metabolic) are involved in the success of human pregnancy and disturbances in any of these processes can lead to fetal loss. Previous studies of our group showed that nuclear receptors in general are involved in this process. The nuclear retinoid X receptor (RXR)—which is involved in cell proliferation, cell differentiation, and organogenesis [3]—is upregulated in recurrent miscarriages [4]. Heterodimer partners are, for example, peroxisome proliferator-activated receptor (PPAR), thyroid hormone receptor (TR), and liver X receptor (LXR) [5,6,7]. PPARγ expression and role are already linked to trophoblast invasion [8, 9] and downregulation of RXRα is discussed as protection against apoptosis [4]; nothing is known about the role of the nuclear oxysterol receptor—the liver X receptor (LXR)—in miscarriage

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