Placental thrombomodulin expression in recurrent miscarriage

<p>Abstract</p> <p>Background</p> <p>Early pregnancy loss can be associated with trophoblast insufficiency and coagulation defects. Thrombomodulin is an endothelial-associated anticoagulant protein involved in the control of hemostasis and inflammation at the vascular beds and it's also a cofactor of the protein C anticoagulant pathway.</p> <p>Discussion</p> <p>We evaluate the Thrombomodulin expression in placental tissue from spontaneous recurrent miscarriage and voluntary abortion as controls. Thrombomodulin mRNA was determined using real-time quantitative polymerase chain reaction. Reduced expression levels of thrombomodulin were found in recurrent miscarriage group compared to controls (1.82-fold of reduction), that corresponds to a reduction of 45% (from control group Delta CT) of thrombomodulin expression in spontaneous miscarriage group respect the control groups.</p> <p>Summary</p> <p>We cannot state at present the exact meaning of a reduced expression of Thrombomodulin in placental tissue. Further studies are needed to elucidate the biological pathway of this important factor in the physiopathology of the trophoblast and in reproductive biology.</p

miR125b1 and TROP2 in preeclampsia complicated by foetal growth restriction: a morphological and biomolecular study

Trophoblast cell surface antigen 2 (TROP2) is a transmembrane glycoprotein originally identified in human trophoblast cell lines and is highly expressed in a variety of epithelial cancers. The TROP2 gene was validated as a direct target of miR-125b1. The purpose of our study was: - to investigate the expression of TROP2 protein in normal placental tissues, in placentas affected by preeclampsia as well as in placentas with preeclampsia complicated by foetal growth restriction (IUGR); - to verify how miR-125b1 was involved in the regulation of TROP2 gene expression. TROP2 protein expression was assessed by immunohistochemistry and quantitative western blotting analyses while miR-125b1 expression was detected by quantitative real-time PCR. The studies were made in normal and pathologic placental tissues. Increasing expression of TROP2 was detected in physiological placental tissue, in according with the increasing gestational age. Probably, it means that TROP2 is related with the differentiation of the cytotrophoblast in syncytiotrophoblast, that occurs during the development of placenta. Moreover, miR-125b1 showed an unchanged expression during normal pregnancy. Higher expression of TROP2 protein was detected in placental tissues collected from patients with preeclampsia complicated by foetal growth restriction, compared with those from preeclampsia and gestational age-matched control samples. The miR-125b1 expression in samples from placentas affected by preeclampsia complicated by IUGR was detected higher than in normal placentas and in placentas affected by preeclampsia. These results suggest that miR-125b1 is not involved I the overproduction of the TROP2 mRNA although the high expression of the miRNA. Our study suggests a possible involvement of TROP2 in the differentiation of the syncytiotrophoblast from villous cytotrophoblast and a possible role of this protein in preeclampsia complicated by foetal growth restriction

HtrA1 in differentiation and growth of human placental tissues

HtrA1 is a secreted multidomain protein with serine protease activity. We used immunohistochemistry, western blotting, real time PCR and ELISA techniques to analyse the role of HtrA1 in normal and pathological development of human placental villous trees. In addition, we evaluated the alterations of maternal plasma HtrA1 level in preeclampsia (PE) complicated by intrauterine growth restriction (IUGR). HtrA1 is expressed in the mesenchymal villi which are considered the basis of growth and differentiation of the villous trees and in the villous stroma directly opposed to cell islands and cell columns in first trimester placentas. In addition, the villous trophoblast, the syncytial knots and the foetal vessels are stained for HtrA1 in first as well as third trimester placentas [1]. When the placenta escapes the normal differentiation and growth control mechanisms, which are present during normal pregnancy, it may develop gestational diseases, such as trophoblastic disease as well as PE and IUGR [1,2]. The most striking finding of our investigation is the decrease of this protease in placental tissues with increasing severity of gestational diseases and the increase of HtrA1 in maternal plasma of PE complicated by IUGR [3]. Based on these data HtrA1 could be considered as a possible marker of an occurring IUGR in preeclamptic women

TGF beta family members function in uterine healthy and fibrotic smooth muscle cells

Uterine leiomyomas are the most common benign tumors of fertile women and the most common indication for hysterectomy. Despite the high prevalence, significant health problems, and huge economical impact on the healthcare system, relatively little is understood about the etiology and pathophysiology of uterine leiomyoma (1). Consequently, medical treatments are still limited (2). The role of the growth factors as ultimate mediators of the steroids hormone is evident in the modulation of the cell proliferation and the morphological cells appearance (3). Activin-A and myostatin are growth factors belonging to TGF-β super family expressed and acting in myometrial (4,5) and leiomyoma cells (6) We aimed to explore the functions of activin and myostatin in human myometrial and leiomyoma cells. First we tested both Smad and non-Smad signaling pathways by western blot. We found that activin-A and myostatin can activate only Smad signaling pathway in both myometrial and leiomyoma cells. Next we explored the effect on cell proliferation and on fibrotic phenotype. We found that activin-A and myostatin are able to suppress primary myometrial cell proliferation but they cannot alter the proliferation of leiomyoma cells. In the next step, we found that activin-A can significantly increase fibronectin expression in leiomyoma cells. Those above results suggest that activin-A and myostatin may express antiproliferative and/or fibrotic effects depending on the cell types by activating Smad signaling pathway

Diabetes during Pregnancy: A Transgenerational Challenge

: For many years, gestational diabetes mellitus (GDM) has been defined as "a glucose intolerance of variable magnitude that begins or is first diagnosed in pregnancy" and that, in most cases, resolves after delivery [...]

Cesarean Section Revealing an Unsuspected Renal Angiomyolipoma in a Woman with Severe Hypertension During Pregnancy: A Case Report

Renal angiomyolipomas are uncommon during pregnancy, but it is important to consider them in the differential diagnosis, for the increased risk of complications such as bleeding, renal artery compression, and renovascular hypertension