RXRα is upregulated in first trimester endometrial glands of spontaneous abortions unlike LXR and PPARγ

Abstract

Nuclear receptors are necessary for uterine invasion of the trophoblast and therefore important for maintaining a viable pregnancy. The aim of this study was to investigate the expression pattern and frequency of LXR, PPARγ and RXRα under physiological circumstances and in spontaneous abortions in endometrial glands and decidual tissue cells. A total of 28 (14 physiologic pregnancies/14 spontaneous abortion) human pregnancies in first trimester were analysed for expression of the nuclear receptors LXR, RXRα and PPARγ. Expression changes were evaluated by immunohistochemistry in decidual tissue and endometrial glands of the decidua. RXRα expression was up-regulated in the endometrial glands of spontaneous abortion (P<0.015). Similar up regulation of RXRα was found in decidual tissue (P<0.05). LXR and PPARγ expression was unchanged in spontaneous abortion. Via Correlation analysis we found a trend to positive correlation of LXR and PPARγ (Spearman correlation coefficient r=0.56 P=0.07) in endometrial glands. In decidual tissue, we found significant negative correlation in the control group, for the combination of RXRα and PPARγ (Spearman correlation coefficient r=0.913, P=0.03). Our data show that RXRα expression is increased in miscarriage in endometrial glands and correlation analysis showed that negative correlation between RXRα and PPARγ disappears in miscarriage. This shift is supposable responsible for the loss of regular function in trophoblast and embryonic tissue.

Figure 1.

A) Analysis of LXR and RXRα co-expression in decidua; LXR expression is shown in red, RXRα expression is visualized in green, synchronized expression of both nuclear receptors is shown (yellow, marked by arrows); in addition, to cells showing co-expression, we also found singular expression of LXR (red) and RXRα (green); some nuclei are negative for both receptors (blue); the identification of cell type positive for either LXR or RXRα in the decidua was achieved with HLA-G double staining; HLA-G is a marker exclusively expressed by extravillous trophoblast cells (EVT). B), HLA-G expression in green and LXR expression in red are shown; the border between decidual stroma cells and the EVT is shown as a discontinuous line; both decidual stroma cells and EVT express LXR. C) HLA-G expression in green and RXRα expression in red are shown; the border between decidual stroma cells and the EVT is shown as a discontinuous line; both decidual stroma cells and EVT express RXRα.

Figure 2.

Immunohistochemical pictures of nuclear expression in endometrial glands: RXRα expression of spontaneous abortion (A) is significantly increased in comparison to RXR expression of control placentas (B). The expression of PPARγ (D,E) and LXR (G,H) was unchanged in spontaneous miscarriage in endometrial glands. Box plots representing the semiquantitative analysis of the expression of different nuclear receptors (C, RXRα; F, PPARγ; I, LXR) in endometrial glands of spontaneous abortion and control placentas derived immunohistochemically. The boxes display the range between the 25^th and 75^th percentile and the black horizontal line indicates the median. The bars represent the 5^th and 95^th percentiles. Circles indicate values, which are more than 1.5 times the box length. The y-axis represents the IRS score.

Figure 3.

Immunohistochemical pictures of nuclear expression in decidual tissue: the number of RXRα expressing decidual stromal cells of spontaneous abortion (A) is significantly increased in comparison to the number of RXRα expressing cells in the decidua of control placentas (B). The expression of PPARγ (D,E) and LXR (G,H) remained unchanged in spontaneous miscarriage Box plots representing the semiquantitative analysis of expression of the different nuclear receptors (C, RXRα; F, PPARγ; I, LXR) in decidual tissue of spontaneous abortion and control placentas derived immunohistochemically. The boxes display the range between the 25^th and 75^th percentile and the black horizontal line indicates the median. The bars represent the 5^th and 95^th percentiles. Circles indicate values, which are more than 1.5 times the box length. The y-axis represents the IRS score.