Morphological changes of placental syncytium and their implications for the pathogenesis of preeclampsia.

Preeclampsia is a hypertensive disease that complicates many pregnancies, typically presenting with new-onset or worsening hypertension and proteinuria. It is well recognized that the placental syncytium plays a key role in the pathogenesis of preeclampsia. This review summarizes the findings pertaining to the structural alterations in the syncytium of preeclamptic placentas and analyzes their pathological implications for the development of preeclampsia. Changes in the trophoblastic lineage, including those in the proliferation of cytotrophoblasts, the formation of syncytiotrophoblast through cell fusion, cell apoptosis and syncytial deportation, are discussed in the context of preeclampsia. Extensive correlations are made between functional deficiencies and the alterations on the levels of gross anatomy, tissue histology, cellular events, ultrastructure, molecular pathways, and gene expression. Attention is given to the significance of dynamic changes in the syncytial turnover in preeclamptic placentas. Specifically, experimental evidences for the complex and obligatory role of syncytin-1 in cell fusion, cell-cycle regulation at the G1/S transition, and apoptosis through AIF-mediated pathway, are discussed in detail in the context of syncytium homeostasis. Finally, the recent observations on the aberrant fibrin deposition in the trophoblastic layer and the trophoblast immature phenotype in preeclamptic placentas and their potential pathogenic impact are also reviewed.

Recombinant HE4 protein promotes proliferation of pancreatic and endometrial cancer cell lines.

Pancreatic adenocarcinoma is one of the most deadly malignancies, and endometrial cancer represents the most common gynecologic cancer in the USA. Better understanding on the pathologic mechanisms and pathways is required for effective treatment of these malignancies. Recently, human epididymis protein 4 (HE4 or WFDC2), a secretory glycoprotein, was found to be overexpressed in pancreatic and endometrial cancers. In addition, studies have shown that HE4 overexpression in endometrial cancer cell lines led to faster cancer progression in a mouse subcutaneous model. These findings raise a question on the role(s) of secretory, extracellular HE4 in cancer development. In the present study, we found that treatment of pancreatic and endometrial cancer cell lines with purified, extracellular HE4 protein led to a significant increase in cell viability and proliferation. Moreover, extracellular HE4 protein was able to increase DNA synthesis, and modulate the mRNA and protein levels of cell cycle marker PCNA and cell cycle inhibitor p21. These effects appeared to be robust and sustainable and required a relatively low concentration of HE4 protein. The findings indicated the secreted, extracellular HE4 may carry some physiopathological functions. Via paracrine/endocrine actions, circulatory HE4 produced by malignant cells may contribute to pancreatic and endometrial cancer progression and/or metastasis.

Microarray analysis on gene regulation by estrogen, progesterone and tamoxifen in human endometrial stromal cells.

Epithelial stromal cells represent a major cellular component of human uterine endometrium that is subject to tight hormonal regulation. Through cell-cell contacts and/or paracrine mechanisms, stromal cells play a significant role in the malignant transformation of epithelial cells. We isolated stromal cells from normal human endometrium and investigated the morphological and transcriptional changes induced by estrogen, progesterone and tamoxifen. We demonstrated that stromal cells express appreciable levels of estrogen and progesterone receptors and undergo different morphological changes upon hormonal stimulation. Microarray analysis indicated that both estrogen and progesterone induced dramatic alterations in a variety of genes associated with cell structure, transcription, cell cycle, and signaling. However, divergent patterns of changes, and in some genes opposite effects, were observed for the two hormones. A large number of genes are identified as novel targets for hormonal regulation. These hormone-responsive genes may be involved in normal uterine function and the development of endometrial malignancies.

Epigenetic and non-epigenetic regulation of syncytin-1 expression in human placenta and cancer tissues.

Syncytin-1 is a human endogenous retroviral envelope gene (HERVW1) product specifically expressed in placental trophoblasts. By mediating the formation of syncytiotrophoblasts through cell-cell fusion, syncytin-1 plays a critical role for the placental barrier, endocrine and exchange functions. During pregnancy, syncytin-1 expression is dynamically regulated by various pathophysiological factors and pathways. This review summarizes and examines published data on epigenetic and non-epigenetic regulation of syncytin-1 gene expression, with a focus on the changes of syncytin-1 DNA methylation and expression in placental trophoblasts under preeclamptic and hypoxic conditions. The functions of syncytiotrophoblasts, the fusogenic and non-fusogenic activities of syncytin-1, and aberrant activation of syncytin-1 expression in cancer cells are also discussed. New findings on the epigenetic regulation of syncytin-1 in placentas from monozygotic/dichorionic discordant twins are analyzed. The close correlation among changes of DNMTs expression, syncytin-1 gene methylation, and syncytin-1 mRNA levels, in placentas associated with discordant fetal growth indicated a dynamic nature of syncytin-1 regulation.

Intraoperative and postoperative morbidity associated with cystoscopy performed in patients undergoing gynecologic surgery.

OBJECTIVE: The purpose of this study was to evaluate the role of cystoscopy during major gynecologic surgery and to describe an interesting and rare complication that was encountered. STUDY DESIGN: This was an observational descriptive study. A retrospective review was performed. Data collected included intraoperative lower urinary tract injuries, injuries that were related directly to cystoscopy, and postoperative morbidity. RESULTS: One hundred one cases were evaluated. Eight lower urinary tract injuries were noted, 4 of which were detected at cystoscopy and 3 of which (2.97%) were detected intraoperatively before cystoscopy. There was one complication that was linked directly to cystoscopy. There were nine postoperative urinary tract infections. Total cost per case excluding anesthesia time was $54.42. CONCLUSION: Liberal use of cystoscopy in gynecologic surgery is recommended. The procedure is safe, easily learned, and inexpensive to perform.