Changes in Placental CRH, Urocortins, and CRH-Receptor mRNA Expression Associated with Preterm Delivery and Chorioamnionitis

abstract Context: The pathogenesis of preterm delivery (PTD) is not clear, although inflammation/infection play a major role. Corticotropin releasing-hormone (CRH) and Urocortins (Ucns) are involved in the pathophysiology of PTD. Objective: This study evaluates trophoblast mRNA expression of CRH, Ucn, Ucn2, Ucn3, and their receptors [CRH-type 1 receptor (CRH-R1), CRH-R2] in infective conditions. To determine whether infection or glucocorticoids contribute to change their placental mRNA expression, the effects of lipopolysaccharide or dexamethasone was evaluated. Design: Placentas were obtained from spontaneous PTD; premature rupture of membranes (pPROM) and pPROM with chorioamnionitis. Setting: Placental specimens were collected from women receiving perinatal care at our Division of Obstetrics and Gynecology. Patients or Other Participants: Pregnant women delivered preterm were enrolled. Interventions: mRNA expression was evaluated by RT-PCR. Main Outcome Measure: Because CRH and Ucns are involved in immunological functions we evaluated their involvement in PTD with or without infection. Results: CRH, Ucn2, and CRH-R1 mRNA expression were higher, while Ucn and CRHR-2 were lower in pPROM with chorioamnionitis than in PTD and pPROM. Ucn3 mRNA expression was lower in pPROM with and without chorioamnionitis than in PTD. The addition of lipopolysaccharide in trophoblast explants decreased Ucn, Ucn3, and CRH-R2 and increased CRH, Ucn2, and CRH-R1 mRNA expression in a dose-dependent manner. Dexamethasone increased CRH and decreased Ucn2 mRNA expression in a dose dependent manner. Conclusions: Our findings showed a significant impact of pPROM with chorioamnionitis on placental CRH peptides and receptors, suggesting that placental expression of stress-related pathways is activated in infective process

Placenta expresses anti-Müllerian hormone and its receptor: Sex-related difference in fetal membranes

INTRODUCTION: Anti-Müllerian hormone (AMH) is a member of the transforming growth factor-β superfamily, playing a role in sexual differentiation and recruitment. Since a correlation exists between AMH serum levels in cord blood and fetal sex, the present study aimed to identify mRNA and protein expression of AMH and AMHRII in placenta and fetal membranes according to fetal sex. METHODS: Placenta and fetal membranes samples (n = 40) were collected from women with singleton uncomplicated pregnancies at term. Identification of AMH protein in placenta and fetal membranes was carried out by immunohistochemistry and AMH and AMHRII protein localization by immunofluorescence, while mRNA expression was assessed by quantitative real-time PCR. RESULT: AMH and AMHRII mRNAs were expressed by placenta and fetal membranes at term, without any significant difference between males and females. Placental immunostaining showed a syncytial localization of AMH without sex-related differences; while fetal membranes immunostaining was significantly more intense in male than in female fetuses (p < 0,01). Immunofluorescence showed an intense co-localization of AMH and AMHRII in placenta and fetal membranes. DISCUSSION: The present study for the first time demonstrated that human placenta and fetal membranes expresses and co-localizes AMH and AMHRII. Although no sex-related difference was found for the mRNA expression both in placenta and fetal membranes, a most intense staining for AMH in male fetal membranes supports AMH as a gender specific hormon

Impaired CRH and urocortin expression and function in eutopic endometrium of women with endometriosis

7sireservedContext: Women with endometriosis have altered endometrial function. CRH and urocortin (Ucn) are neuropeptides produced by human endometrium and modulate endometrial decidualization. Objective: To evaluate endometrial mRNA expression of CRH and Ucn, their role in in vitro decidualization of cultured human endometrial stromal cells (HESCs) in patients with endometriosis, and the role of CRH receptors (CHR-Rs). Design: Obstetrics and Gynecology, University of Siena. Patients: Endometrial specimens were obtained from patients with and without endometriosis. Interventions: Endometrial biopsy obtained at both phases of menstrual cycle. In vitro decidualization of HESCs collected from endometriosis or control was done in the presence of CRH, Ucn, or CRH receptor type 1 (CRH-R1, antalarmin) or type 2 (CRH-R2, astressin 2b) antagonists. Outcome Measures: Endometrial mRNA expression of CRH and Ucn during endometrial cycle; prolactin, CRH-R1, and CRH-R2 mRNA expression during in vitro decidualization. Results: In healthy women CRH and Ucn expression were significantly higher (P < 0.05) in secretory than in proliferative phase; no differences were observed in endometriotic women. During in vitro decidualization, prolactinmRNAexpressionandrelease inendometriosiswaslowerthanincontrol(P< 0.001). CRHandUcnwereabletosignificantly increase (P<0.01) prolactin releaseonlyin controlgroup; moreover, in this group antalarmin reduced prolactin release (P < 0.01). CRH-R1 mRNA expression increased during in vitro decidualization of HESCs in control (P < 0.01) but not in endometriosis. Conclusions: Women with endometriosis show an impaired endometrial expression of CRH and Ucn mRNA,andtheseneuropeptidesarenomoreactive inmodulatingthein vitrodecidualizationofHESCs, associated with a reduced expression of CRH-R1 mRNA. Copyright © 2011 by The Endocrine Society.mixedNovembri, R.;Borges, L.E.;Carrarelli, P.;Rocha, A.L.;De Pascalis, F.;Florio, P.;Petraglia, F.Novembri, R.; Borges, L. E.; Carrarelli, P.; Rocha, A. L.; De Pascalis, F.; Florio, P.; Petraglia, F

Biochemical and biophysical predictors of the response to the induction of labor in nulliparous postterm pregnancy

Objective: The objective of the study was to evaluate the clinical, sonographic, and hormonal variables that influence the success of labor induction in nulliparous postterm pregnancies. Study Design: Fifty nulliparous women with a single postterm pregnancy receiving a slow-release prostaglandin estradiol pessary were prospectively enrolled, and clinical characteristics were analyzed in relation to success of induction of labor. Clinical, sonographic, and hormonal variables were analyzed by univariate statistical analysis and multivariate logistic regression for the prediction of successful induction.Results: The group of patients delivering within 24 hours differed significantly from the remaining patients by higher Bishop scores, body mass indices, estradiol serum concentrations, estriol to estradiol ratios, and shorter cervices. The combination of cervical length and estriol to estradiol ratio achieved a sensitivity of 100% (95% confidence interval, 71.3–100%) and a specificity of 94.1% (95% confidence interval, 80.3–99.1%).Conclusion: Cervical length and the estriol to estradiol ratio represent good predictive indicators of the response to the induction of labor in postterm pregnancies

Placental and maternal serum activin A in spontaneous and induced labor in late-term pregnancy

Purpose: Feto-placental unit represents an important source of activin A, a member of transforming growth factors-β involved in the mechanisms of labor. No evidences are available on activin A in pregnancies beyond 41 weeks of gestation, where induction of labor is often required. The present study aimed to evaluate activin A maternal serum levels and placental mRNA expression in term and late-term pregnancy, with spontaneous or induced labor, and its possible role to predict the response to labor induction. Methods: Maternal serum samples and placental specimens were collected from women with singleton pregnancy admitted for either term spontaneous labor (n = 23) or induction of labor for late-term pregnancy (n = 41), to evaluate activin A serum levels and placental mRNA expression. Univariate and multivariate analyses on activin A serum levels, maternal clinical parameters, and cervical length were conducted in women undergoing induction of labor. Results: Maternal serum activin A levels and placental activin A mRNA expression in late-term pregnancies were significantly higher than at term. Late-term pregnancies who did not respond to induction of labor showed significantly lower levels of activin A compared to responders. The combination of serum activin A and cervical length achieved a sensitivity of 100% and a specificity of 93.55% for the prediction of successful induction. Conclusion: Late-term pregnancy is characterized by hyperexpression of placental activin A and increased maternal activin A secretion. By combining maternal serum activin A levels with cervical length, a good predictive model for the response to induction of labor was elaborated