دانلود رایگان مقاله بیان کاهش پذیرایی ویتامین D در زنان با عدم بارداری مکرر

Abstract

The multiple functions of vitamin D3 have stimulated interest in the role that this vitamin may play during pregnancy. The present study investigated the expression of the vitamin D receptor (VDR) in women during the first trimester of pregnancy in order to determine whether VDR is associated with recurrent pregnancy loss (RPL). Forty women at 7–10 weeks gestation with RPL and 40 women of similar gestational age with a healthy pregnancy were recruited. VDR mRNA and protein in chorionic villi and decidua were evaluated by immunohistochemistry, confocal laser scanning microscopy (CLSM), western blot, and quantitative real-time polymerase chain reaction. The serum levels of VDR were measured by an enzyme-linked immunosorbent assay. Women with RPL had a significantly weaker expression of VDR mRNA in villi and decidual tissues compared with the control women (both p < 0.0001). Western blot analysis showed an approximately 46% decrease in VDR expression in villi and a 52% decrease in decidua in the RPL vs. the controls. Serum VDR levels were also significantly lower in the RPL group than in the control group (p = 0.003). Compared with the controls, immunohistochemical and CLSM analysis revealed significantly lower VDR expression in villous cytotrophoblasts and stromal cells, as well as in decidual glandular epithelial and stromal cells (all p < 0.05). In conclusion, these observations show that women with RPL have lower levels of VDR expression in chorionic villi, decidua and serum compared with normal pregnant women, suggesting that decreased VDR expression in the first trimester pregnancy may be associated with RPL.

4. Discussion

In this study, the chorionic villous and decidual tissues from first trimester pregnancies co-expressed VDR mRNA and protein. The results of real-time RT-qPCR analysis were consistent with those of the Western blot analysis; specifically, the expression levels of VDR were reduced in the chorionic villi and decidua in the RPL group compared with the controls. Based on the immunohistochemistry and CLSM results, in the first trimester of human pregnancy, VDR is expressed in villous cells, including trophoblasts, villous stromal cells, and vascular endothelial cells, as well as in decidual cells, including stromal, glandular epithelial, and vascular endothelial cells. Furthermore, VDR expression was mostly decreased in cytotrophoblasts, decidual glandular epithelial cells, and villous and decidual stromal cells. These results provide evidence for disrupted VDR metabolic homeostasis in early pregnancy loss. Several recent studies have reported that trophoblast cells are the principal cells expressing VDR in human term placentas [12,14]. VDR protein expression has also been previously demonstrated in isolated cultured human extravillous trophoblasts (EVT) from first trimester placentas [15]. In all of the studies, VDR expression has been mainly addressed in the term placenta or cultured human trophoblasts. However, to our knowledge, this is the first study reporting the expression and distribution of VDR in human chorionic villi and decidua during the first trimester of pregnancy in vivo. Furthermore, this is the first report of a correlation between VDR expression and RPL. The presence of VDR in both villi and decidua indicates that vitamin D metabolism and localized autocrine or paracrine regulatory signaling occurs in the fetal-maternal interface in early human pregnancy.