Maternity and Infant Health Hospital of Changning District

Shanghai, China

Maternity and Infant Health Hospital of Changning District

Shanghai, China

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Wang W.S.,Fudan University | Liu C.,Fudan University | Li W.J.,Maternity and Infant Health Hospital of Changning District | Zhu P.,No 401 Hospital | And 3 more authors.
Placenta | Year: 2014

Introduction Increased estrogen production in placenta towards the end of gestation plays a pivotal role in the onset of human labor. Estrogen transforms myometrium from a quiescent to a contractile status. Glucocorticoids have been shown to induce estrogen production through the transcription factor specificity protein 1 (Sp1)-mediated induction of aromatase transcription upon elevation of cyclic adenosine mono-phosphate (cAMP) level in human placental syncytiotrophoblasts. However, it is unclear how glucocorticoids activate cAMP pathway thereby inducing aromatase expression in human placental syncytiotrophoblasts. Material and methods We investigated this issue in cultured primary human placental syncytiotrophoblasts prepared from placentas collected at term without labor. Results We demonstrated that cortisol (0.01-1 μM) dose-dependently increased corticotropin-releasing hormone (CRH) and human chorionic gonadotropin (hCG) α/β subunit expression and their production in the syncytiotrophoblasts. The induction of intracellular cAMP level, Sp1 expression, Sp1 enrichment at the aromatase promoter as well as aromatase expression by cortisol could be partially attenuated by either hCG antibody (1:100) or CRH receptor antagonist α-helical-CRH (1 μM), and further attenuated by combination of hCG antibody and α-helical-CRH. Conclusions Cortisol increases aromatase expression via induction of CRH and hCG production and subsequent elevation of cAMP level and enrichment of Sp1 at the aromatase promoter in human placental syncytiotrophoblasts. These findings may account for the parallel increases of cortisol and estrogen production prior to the onset of parturition. © 2013 Elsevier Ltd. All rights reserved.


PubMed | Fudan University, Maternity and Infant Health Hospital of Changning District, Shanghai JiaoTong University and No 401 Hospital
Type: Journal Article | Journal: Placenta | Year: 2013

Increased estrogen production in placenta towards the end of gestation plays a pivotal role in the onset of human labor. Estrogen transforms myometrium from a quiescent to a contractile status. Glucocorticoids have been shown to induce estrogen production through the transcription factor specificity protein 1 (Sp1)-mediated induction of aromatase transcription upon elevation of cyclic adenosine mono-phosphate (cAMP) level in human placental syncytiotrophoblasts. However, it is unclear how glucocorticoids activate cAMP pathway thereby inducing aromatase expression in human placental syncytiotrophoblasts.We investigated this issue in cultured primary human placental syncytiotrophoblasts prepared from placentas collected at term without labor.We demonstrated that cortisol (0.01-1M) dose-dependently increased corticotropin-releasing hormone (CRH) and human chorionic gonadotropin (hCG) / subunit expression and their production in the syncytiotrophoblasts. The induction of intracellular cAMP level, Sp1 expression, Sp1 enrichment at the aromatase promoter as well as aromatase expression by cortisol could be partially attenuated by either hCG antibody (1:100) or CRH receptor antagonist -helical-CRH (1M), and further attenuated by combination of hCG antibody and -helical-CRH.Cortisol increases aromatase expression via induction of CRH and hCG production and subsequent elevation of cAMP level and enrichment of Sp1 at the aromatase promoter in human placental syncytiotrophoblasts. These findings may account for the parallel increases of cortisol and estrogen production prior to the onset of parturition.


Wang W.,Fudan University | Li J.,Fudan University | Ge Y.,Tongji University | Li W.,Maternity and Infant Health Hospital of Changning District | And 6 more authors.
Endocrinology | Year: 2012

One of the dominant effects of glucocorticoids in triggering parturition in certain animal species is to drive the placental conversion of progesterone to estrogen. However, in the human placenta, estrogen is formed using dehydroepiandrosterone from the fetal adrenal glands rather than progesterone as precursor. Although aromatization of dehydroepiandrosterone is crucial in estrogen synthesis in human placenta, it is not known whether glucocorticoids affect aromatase expression. Human term placental syncytiotrophoblasts were used to examine the effect of cortisol on aromatase expression. The signaling pathway and transcription factors involved were identified in this study. Results showed that cortisol induced aromatase expression in a concentration-dependent manner, which was mediated indirectly by glucocorticoid receptor and required the participation of other proteins. The induction of aromatase by cortisol could be blocked by either specificity protein 1 (Sp1) antagonist mithramycin or knockdown of Sp1 expression. The induction of aromatase and Sp1 by cortisol could be prevented by inhibitors of the cAMP pathway, whereas activators of the cAMP pathway induced Sp1 and aromatase expression as well as Sp1 binding to aromatase promoter. Concomitantly, cortisol treatment and activation of the cAMP pathway led to increased acetylation and decreased methylation of histone 3 at the aromatase promoter. In conclusion, cortisol stimulates aromatase expression through the cAMP/Sp1 pathway in human placental syncytiotrophoblasts. These findings reveal a novel role of cortisol in increasing the local level of estrogen within the placenta that would help transform the myometrium to a contractile state, thereby contributing to a cascade of events leading to human parturition. Copyright © 2012 by The Endocrine Society.


Wang W.,Fudan University | Guo C.,University of Texas Health Science Center at San Antonio | Li W.,Maternity and Infant Health Hospital of Changning District | Li J.,Fudan University | And 3 more authors.
Endocrinology | Year: 2012

Human fetal membranes express 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which reduces biologically inert cortisone to active cortisol and may provide an extraadrenal source of cortisol mediating fetal development and parturition. The reductase activity of 11β-HSD1 depends on the availability of the cofactor reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) derived from the enzymatic activity of hexose-6- phosphodehydrogenase (H6PD). Based on the feed-forward induction of 11β-HSD1 by glucocorticoids in human fetal membranes, we hypothesize that glucocorticoids simultaneously induce H6PD in the fetal membranes. We found a parallel distribution of H6PD and 11β-HSD1 in the amnion, chorion, and decidua. In cultured human amnion fibroblasts, small interfering RNA-mediated knockdown of H6PD expression significantly attenuated the conversion of cortisone to cortisol. Cortisol (0.01-1 μM) induced H6PD expression in a concentration-dependent manner, which was attenuated by glucocorticoid receptor (GR) antagonist RU486. Cortisol induced the expression of p300, a histone acetyltransferase, whereas C646, an inhibitor of p300, attenuated the induction of H6PD by cortisol. Coimmunoprecipitation revealed GR and p300 in the same nuclear protein complex upon cortisol stimulation. Chromatin immunoprecipitation showed that cortisol increased the binding of p300 and GR to H6PD promoter and the acetylation of histone 3 lysine 9 on the promoters. In conclusion, the induction of H6PD by cortisol requires the participation of GR and p300 as well as the acetylation of H3K9 by p300. This may be a prerequisite for the parallel induction of reductase activity of 11β-HSD1 in human amnion fibroblasts in a feed-forward loop that may influence fetal development and the onset of parturition. Copyright © 2012 by The Endocrine Society.


Guo C.,Fudan University | Ni X.,Fudan University | Zhu P.,No 401 Hospital | Li W.,Maternity and Infant Health Hospital of Changning District | And 2 more authors.
Reproduction | Year: 2010

Cytosolic phospholipase A2α (cPLA2α, now known as PLA2G4A) is the enzyme catalyzing the formation of the rate-limiting substrate, arachidonic acid, for prostaglandin (PG) synthesis. The increasing expression of PLA2G4A toward termgestation in human amnion fibroblasts is believed to be the crucial event in parturition. Human amnion fibroblasts produce cortisol, progesterone and express glucocorticoid receptor (GR), progesterone receptorA (PGRA) format term. The roles of progesterone and PGRA in the induction of PLA2G4A by cortisol via GR in the amnion fibroblasts remain largely unknown. Using cultured human term amnion fibroblasts, we found that cortisol induced the expression of PGRA, which was attenuated by inhibiting PG synthesis with indomethacin. Knockdown of PGRA expression or inhibition of endogenous progesterone production with trilostane significantly enhanced the induction of PLA2G4A by cortisol, whereas overexpression of PGRA attenuated the induction of PLA2G4A by cortisol. Although exogenous progesterone did not alter PLA2G4A expression under basal conditions, it attenuated cortisol-induced PLA2G4A expression at concentrations about tenfold higher, which might be achieved by competition with cortisol for GR. In conclusion, PGRA in the presence of endogenous progesterone is a transdominant repressor of the induction of PLA2G4A by cortisol. High level of progesterone may compete with cortisol for GR, thus further inhibiting the induction of PLA2G4A by cortisol. Moreover, increased PG synthesis by cortisol may feed back on the expression of PGRA leading to attenuation of cortisol-induced PLA2G4A expression. The above findings may be pertinent to the inconsistent effects of glucocorticoids on parturition in humans. © 2010 Society for Reproduction and Fertility.


Xu S.-J.,Fudan University | Zhou Y.-Q.,Maternity and Infant Health Hospital of Changning District | Sun L.,Fudan University | Sui L.,Fudan University | And 3 more authors.
Fudan University Journal of Medical Sciences | Year: 2013

Objective: To discuss the application and clinical value of two-dimentional (2D) and three-dimentional (3D) transvaginal ultrasound in the diagnosis and treatment of septate uterus. Methods: We collected 98 patients suspected sepate uterus (including incomplete and complete sepate uterus) by 2D transvaginal ultrasound in Huangpu branch of our hospital from Jan. to Dec. of 2010, whom also underwent hysteroscopy, to diagnose the uterine anomalies. Of the 98 patients, 41 patients also underwent 3D transvaginal ultrasound scanning. We analyzed the accuracy and feasibility of 2D and 3D transvaginal ultrasond in the diagnosis of septateuterus. Results: The diagnosis accordance rate of 2D transvaginal ultrasound was 82.65% (81/98). The diagnosis accordance rate of 3D transvaginal ultrasound was 100% (41/41). Conclusions: 2D Transvaginal ultrasound permits a well assessment in the diagnosis of septate uterus. 3D Transvaginal ultrasound permits a better assesment in the diagnosis of septate uterus.

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