Kumiko Temma-Asano

Oxidative stress-induced S100B protein from placenta and amnion affects soluble Endoglin release from endothelial cells.

Oxidative stress with elevated intracellular Ca(2+) concentration as well as endothelial dysfunction is a component of pre-eclampsia. Our aim was to investigate the oxidative stress-dependent expression of Endoglin and Ca(2+)-binding S100B protein from villous and amniotic tissue cultures, and to assess sEng expression from S100B protein-stimulated endothelial cells. We initially examined Endoglin and Hydroxy-nonenal-(HNE)-modified proteins in the placentas and amnion obtained from women with pre-eclampsia (n = 8), and healthy controls (n = 8) by immunohistochemistry. To examine oxidative stress and the S100B protein effect on sEng expression from endothelial cells, normal villous and amniotic tissue cultures were stimulated by 4-HNE, sodium fluoride and xanthine/xanthine oxidase, whereas human umbilical vein endothelial cell cultures were treated with S100B protein in a dose- and time-dependent manner at 37 degrees C in an environment of 95% air and 5% of CO(2). Culture supernatants were assessed using ELISA. Cell viability was determined using MTS assay. The concentrations of sEng and S100B protein were significantly increased in the villous and amniotic tissue culture supernatants under oxidative stress. S100B protein-stimulated endothelial cells released sEng into conditioned media with a significantly higher expression levels at a concentration of 200 pM-20 nM S100B by 2 h, whereas treated with 200 nM of S100B endothelial cells significantly expressed sEng by 12 h and stimulated the cell proliferation by the same period of time. Our findings show that oxidative stress affects sEng and S100B protein expression from villous and amniotic tissues, and picomolar and low nanomolar concentrations of S100B protein significantly up-regulate sEng release from endothelial cells leading to endothelial dysfunction.

Calcineurin/NFAT pathway: a novel regulator of parturition.

Problem  The oxytocin (OT)–oxytocin receptor (OTR) system plays an important role in mammalian parturition. However, we found OTR‐deficient (OTRKO) mice are fertile and deliver at term without birth defects, thus alternative pathways inducing parturition can be hypothesized.

ORIGINAL ARTICLE: Calcineurin/NFAT Pathway: A Novel Regulator of Parturition

Problem  The oxytocin (OT)–oxytocin receptor (OTR) system plays an important role in mammalian parturition. However, we found OTR‐deficient (OTRKO) mice are fertile and deliver at term without birth defects, thus alternative pathways inducing parturition can be hypothesized.

The expression of fractalkine in the endometrium during the menstrual cycle

The objective of the study was to evaluate the presence of fractalkine in the endometrium of the uterus and the change of fractalkine protein levels during menstrual cycle.

Fractalkine in the peritoneal fluid of women with endometriosis

Objective: The objective of this study was to evaluate the presence of fractalkine in the ascites and the association between fractalkine levels in the ascites and endometriosis. Methods: Peritoneal fluids and peripheral blood samples were obtained from patients undergoing laparoscopy for infertility work‐up or laparoscopic cystectomy. Three samples of peritoneum were obtained from patients undergoing hysterectomy. Western blotting, RT‐PCR and immunohistochemistry were performed. Results: Fractalkine protein was detected in the ascites. Positive staining was confirmed in peritoneal surface cells and perivascular cells of the peritoneum. CX3CR1 positive cells were present in the cells in the peritoneal fluid. The fractalkine concentrations in the ascites of patients with endometriosis were lower than those without endometriosis. There was no significant difference between serum fractalkine levels in patients with and without endometriosis. Conclusion: The decreased level of fractalkine found in the peritoneal fluid of patients with endometriosis may contribute to the pathogenesis of endometriosis.

Effects of 4-Hydroxy-2-Nonenal, a Major Lipid Peroxidation-Derived Aldehyde, and N-Acetylcysteine on the Cyclooxygenase-2 Expression in Human Uterine Myometrium

Background: Chorioamnionitis is one of the important causes of preterm labor. Preterm labor with chorioamnionitis is associated with oxidative stress. We reported that 4-hydroxy-2-nonenal (4-HNE), a major end product of oxidative fatty acid metabolism, is accumulated in the placenta with chorioamnionitis. The aim of this study was to confirm the effect of 4-HNE on cyclooxygenase-2 (COX-2) and prostaglandin (PG) induction in the uterine myometrial tissues. We also examined the effect of N-acetylcysteine (NAC) on 4-HNE-induced COX-2 expression. Methods: Uterine myometrial tissues were obtained from 5 patients. One of them underwent elective cesarean section without labor, and 4 of them underwent hysterectomy because of placental previa or atonic bleeding. We stimulated the uterine myometrial tissues with 4-HNE. In addition, the tissues were pretreated with NAC before 4-HNE treatment. The expression of COX-2 mRNA was observed by real-time PCR. PGE2 and prostacyclin release into the supernatants of the tissue cultures was measured by ELISA. Results: 4-HNE induced the COX-2 mRNA expression and PGE2 production in the uterine myometrial tissue culture in a dose-dependent and time-dependent manner. NAC inhibited 4-HNE-induced COX-2 expression. Conclusion: 4-HNE may play an important role in preterm labor. NAC might be protective against preterm labor under oxidative stress.

ORIGINAL ARTICLE: Calcineurin/NFAT Pathway: A Novel Regulator of Parturition: CALCINEURIN/NFAT PATHWAY AT PARTURITION

Problem  The oxytocin (OT)–oxytocin receptor (OTR) system plays an important role in mammalian parturition. However, we found OTR‐deficient (OTRKO) mice are fertile and deliver at term without birth defects, thus alternative pathways inducing parturition can be hypothesized.