The rate of twin pregnancies has increased over the last decades, largely because of the ongoing ... more The rate of twin pregnancies has increased over the last decades, largely because of the ongoing development of assisted reproductive technology and increased maternal age at childbearing. Twins have a higher risk of adverse outcomes during pregnancy and the perinatal period. The prevalence of umbilical cord abnormalities is higher for twin pregnancies compared with singleton pregnancies. Some of these abnormalities are nonspecific to twinning and can also be found in singleton gestations (such as velamentous cord insertion, vasa previa, and single umbilical artery). Other abnormalities are associated with monochorionic twins, such as umbilical cord entanglement, and umbilical proximate cord insertion. Most of these abnormalities can be detected by ultrasound evaluation. The early and accurate ultrasound diagnosis of chorionicity, amnionicity, and placental and umbilical cord characteristics is crucial if we are to predict the risk of complications and to determine the best manageme...
Les pertes sanguines normales, qui sont de 500 ml, n’entraînent que peu ou pas de modifications h... more Les pertes sanguines normales, qui sont de 500 ml, n’entraînent que peu ou pas de modifications hémodynamiques chez les parturientes. En revanche, l’hémorragie grave définie comme un saignement de plus de 1000 ml se traduit par des manifestations cliniques plus bruyantes, est grevée d’une morbidité importante et d’une mortalité non négligeable. Dans la grande majorité des cas, les hémorragies diagnostiquées et dont la cause est identifiée répondent heureusement aux traitements de première intention, incluant utérotoniques, révision de la filière génitale et sutures en association avec une réanimation médicale adaptée. Il arrive cependant dans moins de 1 % des accouchements que ces mesures soient insuffisantes et que la poursuite des saignements associée aux altérations de l’hémostase et de l’hémodynamique imposent de recourir à d’autres modalités thérapeutiques. Ces recours ultimes sont représentés par l’hystérectomie d’hémostase, les ligatures vasculaires et l’embolisation artériel...
Insufficient remodeling of uterine arteries causes pregnancy‐related diseases, including fetal gr... more Insufficient remodeling of uterine arteries causes pregnancy‐related diseases, including fetal growth restriction and preeclampsia. In these situations, reduced maternal blood flow in the placenta is thought to be responsible for the persistence of a low oxygen environment throughout pregnancy. We hypothesized that chronic activation of transcription factors hypoxia‐inducible factors (HIFs) actively participates in placental underdevelopment, which impairs fetal growth. The computer‐assisted analysis in pathological placentas revealed an increased number of HIF‐2α‐positive nuclei in the syncytium compared to normal human placentas, while HIF‐1α stabilization was unchanged. Specific involvement of HIF‐2α was confirmed in primary human cytotrophoblasts rendered deficient for HIF1A or HIF2A. Silencing HIF2A increased the expression of main syncytialization markers as well as differentiation and syncytium formation. It also improved placental growth factor bioavailability. None of these changes was seen when silencing HIF1A. Conversely, the experimental induction of HIF‐2α expression repressed forskolin‐induced differentiation in BeWo choriocarcinoma cells. Our mechanistic insights evidence that transcription factor HIF‐2α impairs placental function, thus suggesting its participation in fetal growth restriction and preeclampsia when placentas become chronically hypoxic. Furthermore, it suggests the possibility to develop novel molecular targeting therapies for placental dysfunction.
International Journal of Gynecology & Obstetrics, 2019
ObjectiveTo determine whether term fetal membranes from transabdominal cerclage (TAC) patients ha... more ObjectiveTo determine whether term fetal membranes from transabdominal cerclage (TAC) patients have favorable characteristics compared with membranes from patients without TAC.MethodsA prospective study of consecutive pregnant women who had undergone TAC and were delivered by elective cesarean after 37 weeks before the onset of labor at Cliniques universitaires Saint‐Luc, Brussels, between January 2015 and June 2016. Membranes were collected from two areas: overlying the cervix and located far from the cervix. Membrane thickness, 15‐hydroxyprostaglandin dehydrogenase (PGDH), toll‐like receptor‐2 (TLR2) expression, and senescence were measured and compared between the TAC group and a control group without TAC enrolled using the same study criteria.ResultsIn the cervical area of the TAC group, the chorion was significantly thicker (P=0.003). PGDH and TLR2 expression were also significantly increased in the cervical area of the TAC group (P=0.021 and P=0.043, respectively). Senescence ...
Inhibin α (Inha) gene expression is regulated, in rat granulosa cells, via a cyclic 3&amp... more Inhibin α (Inha) gene expression is regulated, in rat granulosa cells, via a cyclic 3',5'-adenosine monophosphate (AMP)-response element (CRE) found in a region of the promoter that is homologous to the human INHA promoter. We previously found that during in vitro cytotrophoblast differentiation, human INHA gene expression was regulated by TFAP2A via association with an AP-2 site located upstream of this CRE. The aim of this study was to evaluate if the human INHA gene was also regulated by cAMP in trophoblasts, and to investigate the possible crosstalk between TFAP2 and cAMP signaling pathways in the regulation of INHA gene expression. Treatment with cAMP or forskolin increased INHA mRNA expression by 7- and 2-fold in primary cytotrophoblasts and choriocarcinoma-derived BeWo cells, respectively. Treatment with the protein kinase A inhibitor H-89 reduced forskolin-induced luciferase activity by ∼40% in BeWo cells transfected with an INHA promoter-driven luciferase reporter vector. TFAP2 overexpression increased basal luciferase activity, whereas the dominant repressor KCREB abolished it. Surprisingly, mutation of the CRE also eliminated the TFAP2-induced transcription, although TFAP2 overexpression was still able to increase forskolin-induced luciferase activity when the AP-2 binding site, but not the CRE site, was mutated. Thus, INHA gene expression is upregulated by cAMP via CRE in human trophoblasts, and TFAP2 regulates this expression by interacting with CRE.
Malformation affecting the genital tract is a rare condition. Enlargement of the mass and specifi... more Malformation affecting the genital tract is a rare condition. Enlargement of the mass and specific complications may occur following hemodynamic changes associated with pregnancy. A 25-year-old pregnant primigravida affected by an extended vulvar and thigh venous malformation with localised intravascular consumptive coagulopathy was referred to our hospital. Her antenatal care was uneventful until term. She underwent an elective caesarean section because the venous malformation location precluded vaginal birth. At 3 days postpartum, she suffered life-threatening bleeding in the abdominal cavity with disseminated intravascular coagulation requiring multiple blood and platelets transfusions as well as transarterial embolisation. The patient recovered and was discharged after 20 days. Specific counselling and management of pregnant patients with large vascular malformations is essential as it is associated with increased complications rate such as peripartal thrombosis and haemorrhages...
info:eu-repo/semantics/publishedAbstracts 7th International Congress of EndocrinologyComm. ibid. ... more info:eu-repo/semantics/publishedAbstracts 7th International Congress of EndocrinologyComm. ibid. - Quebec City (Canada), 03.07.198
The rate of twin pregnancies has increased over the last decades, largely because of the ongoing ... more The rate of twin pregnancies has increased over the last decades, largely because of the ongoing development of assisted reproductive technology and increased maternal age at childbearing. Twins have a higher risk of adverse outcomes during pregnancy and the perinatal period. The prevalence of umbilical cord abnormalities is higher for twin pregnancies compared with singleton pregnancies. Some of these abnormalities are nonspecific to twinning and can also be found in singleton gestations (such as velamentous cord insertion, vasa previa, and single umbilical artery). Other abnormalities are associated with monochorionic twins, such as umbilical cord entanglement, and umbilical proximate cord insertion. Most of these abnormalities can be detected by ultrasound evaluation. The early and accurate ultrasound diagnosis of chorionicity, amnionicity, and placental and umbilical cord characteristics is crucial if we are to predict the risk of complications and to determine the best manageme...
Les pertes sanguines normales, qui sont de 500 ml, n’entraînent que peu ou pas de modifications h... more Les pertes sanguines normales, qui sont de 500 ml, n’entraînent que peu ou pas de modifications hémodynamiques chez les parturientes. En revanche, l’hémorragie grave définie comme un saignement de plus de 1000 ml se traduit par des manifestations cliniques plus bruyantes, est grevée d’une morbidité importante et d’une mortalité non négligeable. Dans la grande majorité des cas, les hémorragies diagnostiquées et dont la cause est identifiée répondent heureusement aux traitements de première intention, incluant utérotoniques, révision de la filière génitale et sutures en association avec une réanimation médicale adaptée. Il arrive cependant dans moins de 1 % des accouchements que ces mesures soient insuffisantes et que la poursuite des saignements associée aux altérations de l’hémostase et de l’hémodynamique imposent de recourir à d’autres modalités thérapeutiques. Ces recours ultimes sont représentés par l’hystérectomie d’hémostase, les ligatures vasculaires et l’embolisation artériel...
Insufficient remodeling of uterine arteries causes pregnancy‐related diseases, including fetal gr... more Insufficient remodeling of uterine arteries causes pregnancy‐related diseases, including fetal growth restriction and preeclampsia. In these situations, reduced maternal blood flow in the placenta is thought to be responsible for the persistence of a low oxygen environment throughout pregnancy. We hypothesized that chronic activation of transcription factors hypoxia‐inducible factors (HIFs) actively participates in placental underdevelopment, which impairs fetal growth. The computer‐assisted analysis in pathological placentas revealed an increased number of HIF‐2α‐positive nuclei in the syncytium compared to normal human placentas, while HIF‐1α stabilization was unchanged. Specific involvement of HIF‐2α was confirmed in primary human cytotrophoblasts rendered deficient for HIF1A or HIF2A. Silencing HIF2A increased the expression of main syncytialization markers as well as differentiation and syncytium formation. It also improved placental growth factor bioavailability. None of these changes was seen when silencing HIF1A. Conversely, the experimental induction of HIF‐2α expression repressed forskolin‐induced differentiation in BeWo choriocarcinoma cells. Our mechanistic insights evidence that transcription factor HIF‐2α impairs placental function, thus suggesting its participation in fetal growth restriction and preeclampsia when placentas become chronically hypoxic. Furthermore, it suggests the possibility to develop novel molecular targeting therapies for placental dysfunction.
International Journal of Gynecology & Obstetrics, 2019
ObjectiveTo determine whether term fetal membranes from transabdominal cerclage (TAC) patients ha... more ObjectiveTo determine whether term fetal membranes from transabdominal cerclage (TAC) patients have favorable characteristics compared with membranes from patients without TAC.MethodsA prospective study of consecutive pregnant women who had undergone TAC and were delivered by elective cesarean after 37 weeks before the onset of labor at Cliniques universitaires Saint‐Luc, Brussels, between January 2015 and June 2016. Membranes were collected from two areas: overlying the cervix and located far from the cervix. Membrane thickness, 15‐hydroxyprostaglandin dehydrogenase (PGDH), toll‐like receptor‐2 (TLR2) expression, and senescence were measured and compared between the TAC group and a control group without TAC enrolled using the same study criteria.ResultsIn the cervical area of the TAC group, the chorion was significantly thicker (P=0.003). PGDH and TLR2 expression were also significantly increased in the cervical area of the TAC group (P=0.021 and P=0.043, respectively). Senescence ...
Inhibin α (Inha) gene expression is regulated, in rat granulosa cells, via a cyclic 3&amp... more Inhibin α (Inha) gene expression is regulated, in rat granulosa cells, via a cyclic 3',5'-adenosine monophosphate (AMP)-response element (CRE) found in a region of the promoter that is homologous to the human INHA promoter. We previously found that during in vitro cytotrophoblast differentiation, human INHA gene expression was regulated by TFAP2A via association with an AP-2 site located upstream of this CRE. The aim of this study was to evaluate if the human INHA gene was also regulated by cAMP in trophoblasts, and to investigate the possible crosstalk between TFAP2 and cAMP signaling pathways in the regulation of INHA gene expression. Treatment with cAMP or forskolin increased INHA mRNA expression by 7- and 2-fold in primary cytotrophoblasts and choriocarcinoma-derived BeWo cells, respectively. Treatment with the protein kinase A inhibitor H-89 reduced forskolin-induced luciferase activity by ∼40% in BeWo cells transfected with an INHA promoter-driven luciferase reporter vector. TFAP2 overexpression increased basal luciferase activity, whereas the dominant repressor KCREB abolished it. Surprisingly, mutation of the CRE also eliminated the TFAP2-induced transcription, although TFAP2 overexpression was still able to increase forskolin-induced luciferase activity when the AP-2 binding site, but not the CRE site, was mutated. Thus, INHA gene expression is upregulated by cAMP via CRE in human trophoblasts, and TFAP2 regulates this expression by interacting with CRE.
Malformation affecting the genital tract is a rare condition. Enlargement of the mass and specifi... more Malformation affecting the genital tract is a rare condition. Enlargement of the mass and specific complications may occur following hemodynamic changes associated with pregnancy. A 25-year-old pregnant primigravida affected by an extended vulvar and thigh venous malformation with localised intravascular consumptive coagulopathy was referred to our hospital. Her antenatal care was uneventful until term. She underwent an elective caesarean section because the venous malformation location precluded vaginal birth. At 3 days postpartum, she suffered life-threatening bleeding in the abdominal cavity with disseminated intravascular coagulation requiring multiple blood and platelets transfusions as well as transarterial embolisation. The patient recovered and was discharged after 20 days. Specific counselling and management of pregnant patients with large vascular malformations is essential as it is associated with increased complications rate such as peripartal thrombosis and haemorrhages...
info:eu-repo/semantics/publishedAbstracts 7th International Congress of EndocrinologyComm. ibid. ... more info:eu-repo/semantics/publishedAbstracts 7th International Congress of EndocrinologyComm. ibid. - Quebec City (Canada), 03.07.198
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