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.

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. METHODS OF STUDY: We tested the gene expression profile of OTRKO mice using suppressive subtractive hybridization, and focused on the calcineurin/nuclear factor of activated T cells (NFAT) pathway. We examined the expression and localization of this pathway in mouse parturition. RESULTS: Calcineurin and NFATc1 were detected in the decidua of pregnant uteri at term using immunohistochemistry (IHC). We identified higher activation levels of NFATc1 in wild type (WT) than in OTRKO mice and increased calcineurin A and NFATc1 mRNA levels during pregnancy. Moreover, injection of FK506, the inhibitor of this pathway, prolonged the delivery of the first pup. CONCLUSION: Our findings suggested that the calcineurin/NFAT pathway might play a substantial role in initiation of labor.

Prospective study of non-closure or closure of the peritoneum at cesarean delivery in 124 women: Impact of prior peritoneal closure at primary cesarean on the interval time between first cesarean section and the next pregnancy and significant adhesion at second cesarean.

AIM: The aim of this study was to evaluate the effect of non-closure of the peritoneum at cesarean delivery on postoperative complications and the interval time to the next pregnancy, and to investigate the incidence of adhesion following cesarean and the association between adhesion formation and peritoneal closure. METHODS: One hundred and twenty four women scheduled for cesarean section were randomized to either closure of both the visceral and parietal peritoneum (C-group, n = 70) or non-closure (NC-group, n = 54). At repeated cesarean, the levels and extent of adhesion, operating time, and any complications were examined. RESULTS: There was no difference in the incidence of postoperative complications at the first cesarean section. The operating time of the C-group was significantly longer than that of the NC-group. The frequency of analgesic use was significantly higher in the C-group. The time interval from cesarean section to the next pregnancy in the NC-group was significantly shorter than that in the C-group. There are no significant differences between the rates of complications in the C-group and the NC-group at repeated cesarean. The incidence of adhesion in the C-group was significantly higher than that in the NC-group (P < 0.05). The mean total operating time and the mean interval time for skin incision to delivery in the C-group were significantly longer than those in the NC-group (P < 0.05 and P < 0.001, respectively) at repeated cesarean section. CONCLUSIONS: Non-closure of the peritoneum at cesarean delivery appears to have no adverse effect on postoperative recovery, it also decreases the number of analgesic doses and shortens the operating time and may be more desirable in achieving a next pregnancy. The present study demonstrated that surgical peritoneal closure resulted in more advanced adhesion formation. The practice of non-closure of the peritoneum should be performed at cesarean.

Simple and highly efficient method for transient in vivo gene transfer to mid-late pregnant mouse uterus.

Up- and down-regulation of various genes in the placenta, decidua and amnion has been reported during the mid-late period of pregnancy and in pregnancy-related complications, such as preeclampsia and preterm labor. However, whether this gene regulation at the feto-maternal interface directly influences the physiology/pathophysiology of disease remains unknown. In order to study this problem, transient gene transfer into the pregnant uterus at mid-late term would be a useful tool. We injected exogenous plasmid entrapped using a commercially available Hemagglutinating Virus of Japan Envelope (HVJ-E) vector system (GenomONE Neo, Ishihara Sangyo) into the extra-amniotic space of the upper part of the pregnant mouse uterus on day 14.5 post-coitus (p.c.). Luciferase activity driven by the cytomegalovirus promoter was detectable for 3 days after transfection in the upper, middle and lower part of the uterus. beta-Galactsidase activity was localized in the basal lamina of the placenta, the decidual membrane and the fetal membrane. Exogenous plasmid was not transmitted to the fetus. The course of pregnancy was not disturbed by this procedure; rupture of membranes, intrauterine fetal growth restriction and preterm birth were not observed. Thus, we demonstrated that this transient gene transfer method is highly efficient and minimally invasive, and expect that this procedure will be a useful tool to analyze the pathophysiology of pregnancy-related disorders.

MR imaging evaluation of postmenopausal adnexal masses: correlation with final pathologic diagnosis.

OBJECTIVE: Adoption of transvaginal ultrasound in usual clinical settings allowed us to find asymptomatic adnexal masses more frequently in postmenopausal women. These masses were traditionally considered as the indication of surgical excision to determine histological diagnosis. Recently, if the appearance of that is simple cyst, conservative management may be acceptable because ultrasound benign diagnosis is proved to be reasonably reliable. We investigate here the reliability of benign diagnosis by MR imaging with gadolinium enhancement for both of simple and complex postmenopausal adnexal cystic masses. METHOD: We retrospectively examined the data of 121 postmenopausal patients who underwent surgery during a 3-years-period (from January, 2000 to December 2002) for adnexal mass under diagnosis of benign adnexal cysts based on MR imaging. RESULTS: Pathological examination identified two cases of malignancy among 121 cases diagnosed as benign by MR imaging. Among the cysts that revealed a simple pattern by MR imaging, 64/66 cases (97.0%) were benign histology and among the cysts that showed a complex pattern by MR imaging, 55/55 cases (100%) were benign histology. Among the cysts with diameter less than or equal to 10cm, 48/49 simple cysts and 32/32 complex cysts were benign histology. CONCLUSIONS: The diagnosis of benign adnexal mass in postmenopausal women by MR imaging was reliable. Conservative observation for postmenopausal patients of asymptomatic and small cysts under benign diagnosis based on MR imaging with gadolinium enhancement will be feasible even if the cysts appearances are complex, with careful follow-up program.