Cathy Vaillancourt - Academia.edu (original) (raw)
Papers by Cathy Vaillancourt
ACS Applied Materials & Interfaces, 2019
The placental syncytiotrophoblast is a giant multinucleated cell that forms a tree-like structure... more The placental syncytiotrophoblast is a giant multinucleated cell that forms a tree-like structure and regulates transport between mother and baby during development. It is maintained throughout pregnancy by continuous fusion of trophoblast cells, and disruptions in fusion are associated with considerable adverse health effects including diseases such as preeclampsia. Developing predictive control over cell fusion in culture models is hence of critical importance in placental drug discovery and transport studies; but this can currently be only partially achieved with biochemical factors. Here, we investigate whether biophysical signals associated with budding morphogenesis during development of the placental villous tree can synergistically direct and enhance cultured trophoblast fusion. We use micropatterning techniques to manipulate physical stresses in engineered microtissues, and demonstrate that biomimetic geometries simulating budding robustly enhances fusion and alter spatial patterns of synthesis of pregnancy-related hormones. These findings indicate that biophysical signals play a previously unrecognized and significant role in regulating placental fusion and function, in synergy with established soluble signals. More broadly, our studies demonstrate that biomimetic strategies focusing on tissue mechanics can be important approaches to design, build, and test placental tissue cultures for future studies of pregnancy-related drug safety, efficacy and discovery.
Journal of Pineal Research, 2018
Melatonin has been proposed as a possible treatment for the deleterious effects of hypoxia/reoxyg... more Melatonin has been proposed as a possible treatment for the deleterious effects of hypoxia/reoxygenation (H/R), such as autophagy, inflammation, and apoptosis. Pathological pregnancies, such as preeclampsia, are associated with placental H/R, and decreased placental melatonin synthesis as well as lower melatonin levels in the placenta and maternal plasma. However, the effects of exogenous melatonin on inflammation and autophagy induced by pregnancy complications associated with H/R await investigation. This study aimed to determine as to whether melatonin protects human primary villous trophoblasts against H/R‐induced autophagy, inflammation, and apoptosis. Human primary villous cytotrophoblasts were isolated and immunopurified from normal term placentas. These cells were then exposed or not to 1 mmol/L melatonin for 72 hour in normoxia (8% O2), thereby inducing differentiation into syncytiotrophoblast that was then exposed to H/R (0.5% O2, for 4 hour) or normoxia. H/R decreased end...
Enfances, Familles, Générations
Cadre de la recherche : Bien que tous les résidents du Québec aient été affectés par la pandémie ... more Cadre de la recherche : Bien que tous les résidents du Québec aient été affectés par la pandémie de la COVID-19 et par les mesures sanitaires et sociales mises en place depuis le 13 mars 2020, les parents occupant un emploi rémunéré ont été particulièrement affectés par les différents stresseurs engendrés par cette crise, et ce, tant dans leur vie familiale que professionnelle. Dans un tel contexte, il apparaît pertinent de se pencher sur les conséquences engendrées par la pandémie sur la conciliation travail-famille, et plus particulièrement sur les facteurs qui y sont associés. Objectifs : La présente étude vise à documenter les caractéristiques personnelles, familiales et professionnelles associées à la conciliation travail-famille chez les employés universitaires ayant des enfants âgés de 11 ans ou moins dans le contexte de la pandémie. Méthodologie : Les données utilisées pour la présente étude ont été collectées entre le 24 avril et le 5 juin 2020 par le biais d’un sondage en ...
International Journal of Molecular Sciences
Bile acids (BAs) are natural ligands for several receptors modulating cell activities. BAs are sy... more Bile acids (BAs) are natural ligands for several receptors modulating cell activities. BAs are synthesized via the classic (neutral) and alternative (acidic) pathways. The classic pathway is initiated by CYP7A1/Cyp7a1, converting cholesterol to 7α-hydroxycholesterol, while the alternative pathway starts with hydroxylation of the cholesterol side chain, producing an oxysterol. In addition to originating from the liver, BAs are reported to be synthesized in the brain. We aimed at determining if the placenta potentially represents an extrahepatic source of BAs. Therefore, the mRNAs coding for selected enzymes involved in the hepatic BA synthesis machinery were screened in human term and CD1 mouse late gestation placentas from healthy pregnancies. Additionally, data from murine placenta and brain tissue were compared to determine whether the BA synthetic machinery is comparable in these organs. We found that CYP7A1, CYP46A1, and BAAT mRNAs are lacking in the human placenta, while corres...
Scientific Reports
Selective serotonin reuptake inhibitors (SSRIs) for treatment of prenatal maternal depression hav... more Selective serotonin reuptake inhibitors (SSRIs) for treatment of prenatal maternal depression have been associated with neonatal neurobehavioral disturbances, though the molecular mechanisms remain poorly understood. In utero exposure to SSRIs may affect DNA methylation (DNAme) in the human placenta, an epigenetic mark that is established during development and is associated with gene expression. Chorionic villus samples from 64 human placentas were profiled with the Illumina MethylationEPIC BeadChip; clinical assessments of maternal mood and SSRI treatment records were collected at multiple time points during pregnancy. Case distribution was 20 SSRI-exposed cases and 44 SSRI non-exposed cases. Maternal depression was defined using a mean maternal Hamilton Depression score > 8 to indicate symptomatic depressed mood (“maternally-depressed”), and we further classified cases into SSRI-exposed, maternally-depressed (n = 14); SSRI-exposed, not maternally-depressed (n = 6); SSRI non-e...
Human Molecular Genetics, 2021
Spontaneous preterm birth is a serious medical condition responsible for substantial perinatal mo... more Spontaneous preterm birth is a serious medical condition responsible for substantial perinatal morbidity and mortality. Its phenotypic characteristics, preterm labor with intact membranes (PTL) and preterm premature rupture of the membranes (PPROM), are associated with significantly increased risks of neurological and behavioral alterations in childhood and later life. Recognizing the inflammatory milieu associated with PTL and PPROM, here, we examined expression signatures of placental tryptophan metabolism, an important pathway in prenatal brain development and immunotolerance. The study was performed in a well-characterized clinical cohort of healthy term pregnancies (n = 39) and 167 preterm deliveries (PTL, n = 38 and PPROM, n = 129). Within the preterm group, we then investigated potential mechanistic links between differential placental tryptophan pathway expression, preterm birth and both intra-amniotic markers (such as amniotic fluid interleukin-6) and maternal inflammatory ...
Preeclampsia, 2017
Lack of blood flow and aberrant levels of oxygenation in placentas are recurrent in pregnancy dis... more Lack of blood flow and aberrant levels of oxygenation in placentas are recurrent in pregnancy diseases, such as preeclampsia. These alterations generate situations of hypoxia and hypoxia/reoxygenation (H/R) and consequent oxidative stress, increased cell death, and inflammation in trophoblasts. The models used to understand the effects of hypoxia and H/R on trophoblasts require a rather big structure. This chapter describes the details of a suitable and reasonable approach with hypoxia chambers to expose human placental trophoblasts to variable conditions of oxygenation.
Environmental Health Perspectives, 2019
Challenges, 2019
Work that addresses the cumulative impacts of resource extraction on environment, community, and ... more Work that addresses the cumulative impacts of resource extraction on environment, community, and health is necessarily large in scope. This paper presents experiences from initiating research at this intersection and explores implications for the ambitious, integrative agenda of planetary health. The purpose is to outline origins, design features, and preliminary insights from our intersectoral and international project, based in Canada and titled the “Environment, Community, Health Observatory” (ECHO) Network. With a clear emphasis on rural, remote, and Indigenous communities, environments, and health, the ECHO Network is designed to answer the question: How can an Environment, Community, Health Observatory Network support the integrative tools and processes required to improve understanding and response to the cumulative health impacts of resource development? The Network is informed by four regional cases across Canada where we employ a framework and an approach grounded in obser...
Connections for Health, Ecosystems and Society / The Fifth biennial conference of the Internation... more Connections for Health, Ecosystems and Society / The Fifth biennial conference of the International Association for Ecology and Health, August 11-15, Université du Québec à Montréal (Canada).
Journal of pineal research, 2015
Melatonin is highly produced in the placenta where it protects against molecular damage and cellu... more Melatonin is highly produced in the placenta where it protects against molecular damage and cellular dysfunction arising from hypoxia/re-oxygenation induced oxidative stress as observed in primary cultures of syncytiotrophoblast. However, little is known about melatonin and its receptor in the human placenta throughout pregnancy and their role in villous trophoblast development. The purpose of this study is to determine melatonin synthesizing enzymes; arylalkylamine N-acetyltransferase (AANAT) and hydroxyindole O-methyltransferase (HIOMT), and melatonin receptor (MT1 and MT2) expression throughout pregnancy as well as the role of melatonin and its receptors in villous trophoblast syncytialisation. Our data show that the melatonin generating system is expressed throughout pregnancy (from week 7 to term) in placental tissues. AANAT and HIOMT show maximal expression at the 3(rd) trimester of pregnancy. MT1 receptor expression is maximal at the 1(st) trimester compared to the 2(nd) and ...
Canadian journal of public health = Revue canadienne de santé publique, Jan 7, 2013
From a public health perspective, the follow-up of women during pregnancy and the perinatal perio... more From a public health perspective, the follow-up of women during pregnancy and the perinatal period requires quality communication and health services that take into account the context in which these women live. However, challenges related to access to health services in French in a minority situation have been documented in recent research. The objective of this pilot study is to better understand the perceptions, the lived experiences and the needs of pregnant Francophone women living in Canada within a linguistic minority context. Given the exploratory nature of the inquiry, a mixed method descriptive study was conducted in Alberta and New Brunswick, whose populations are 2% and 33% Francophone, respectively. Two semi-structured interviews and a series of validated questionnaires were administered to 21 pregnant women during the third trimester of pregnancy and at six weeks postnatal. Based on the questionnaires, a descriptive analysis documented participants' characteristics...
Reproductive BioMedicine Online, 2009
Dr Vaillancourt's main research goals are to elucidate the effect of environmental factors, such ... more Dr Vaillancourt's main research goals are to elucidate the effect of environmental factors, such as pollutants, depression and obstetric complications, on placental function and development. Her studies focus on placental dopaminergic, serotoninergic and melatoninergic systems.
Placenta, 2011
It is known that serotonin can influence the production and function of sex hormones, such as est... more It is known that serotonin can influence the production and function of sex hormones, such as estrogens. Estrogens are critical for maintenance of pregnancy and regulate placental and fetal development. The key enzyme controlling estrogens synthesis during pregnancy is placental aromatase (CYP19). To better understand the regulation of placental aromatase, this study determined whether serotonin is involved in the regulation of this enzyme. BeWo and JEG-3 choriocarcinoma cells were used as models of the human placental trophoblast to evaluate the effects of serotonin and selective 5-HT 2A receptor agonists on CYP19 activity and expression. Serotonin and selective 5-HT 2A receptor agonists as well as PKC activation increased aromatase activity and expression in BeWo and JEG-3 cells. Dexamethasone, which regulates aromatase expression via JAK/STAT activation in certain tissues, had no effect. Increased CYP19 gene transcription by 5-HT 2A receptor and PKC stimulation was mediated by activation of the placental I.1 aromatase promoter. This study shows that the serotonergic system modulates placental aromatase expression, which would result in altered estrogens biosynthesis in trophoblast cells. Future detailed studies of serotonineestrogen interactions in placenta are crucial for an improved understanding of the endo-, para-and autocrine role of serotonin during pregnancy and fetal development.
Placenta, 2011
Serotonin 5-HT 2A receptor activation improves viability, increases DNA synthesis and activates J... more Serotonin 5-HT 2A receptor activation improves viability, increases DNA synthesis and activates JAK2-STAT3 and MEK1/2-ERK1/2 signalling pathways in JEG-3 human trophoblast choriocarcinoma cells. The goal of this study was to characterize the signal transduction cascade involved in 5-HT 2A receptorinduced growth of JEG-3 cells. Selective 5-HT 2A receptor agonist, DOI, induced JEG-3 cell growth was inhibited by the inhibitor of JAK2 (AG490), MEK1/2 (U0126), phospholipase C-b (PLC-b; U73122) and protein kinase C-b (PKC-b; Gö6976)), whereas the selective phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002) had no effect. Specific inhibitors of PLC-b, PKC-b and Ras (farnesylthiosalicylic acid) inhibit activation of ERK1/2, whereas the PKC-z inhibitor GF109203X had no effect. Interestingly, inhibition of JAK2 prevented DOI-induced phosphorylation of ERK1/2 whereas inhibition of ERK1/2 pathway had no effect on DOI-induced activation of STAT3. Taken together, our results demonstrate that both the JAK2-STAT3 and PLC-b-PKC-bRas -ERK1/2 signalling pathways are involved in the stimulation of JEG-3 cell growth mediated by DOI. Moreover, this study shows that activation of JAK2 by the 5-HT 2A receptor is essential to activate both STAT3 and ERK1/2 signalling pathways as well as to increase JEG-3 choriocarcinoma cell growth and survival.
Molecular and Cellular Endocrinology, 2012
Melatonin has both the ability to induce intrinsic apoptosis in tumor cells while it inhibits it ... more Melatonin has both the ability to induce intrinsic apoptosis in tumor cells while it inhibits it in non-tumor cells. Melatonin kills tumor cells through induction of reactive oxygen species generation and activation of pro-apoptotic pathways. In contrast, melatonin promotes the survival of non-tumor cells due to its antioxidant properties and the inhibition of pro-apoptotic pathways. In primary human villous trophoblast, a known pseudo-tumorigenic tissue, melatonin promotes the survival through inhibition of the Bax/Bcl-2 pathway while in BeWo choriocarcinoma cell line melatonin induces permeabilization of the mitochondrial membrane leading to cellular death. These findings suggest that the trophoblast is a good model to study the differential effects of melatonin on the intrinsic apoptosis pathway. This review describes the differential effects of melatonin on the intrinsic apoptosis pathway in tumor and non-tumor cells and presents the trophoblast as a novel model system in which to study these effects of melatonin.
Molecular and Cellular Endocrinology, 2013
ACS Applied Materials & Interfaces, 2019
The placental syncytiotrophoblast is a giant multinucleated cell that forms a tree-like structure... more The placental syncytiotrophoblast is a giant multinucleated cell that forms a tree-like structure and regulates transport between mother and baby during development. It is maintained throughout pregnancy by continuous fusion of trophoblast cells, and disruptions in fusion are associated with considerable adverse health effects including diseases such as preeclampsia. Developing predictive control over cell fusion in culture models is hence of critical importance in placental drug discovery and transport studies; but this can currently be only partially achieved with biochemical factors. Here, we investigate whether biophysical signals associated with budding morphogenesis during development of the placental villous tree can synergistically direct and enhance cultured trophoblast fusion. We use micropatterning techniques to manipulate physical stresses in engineered microtissues, and demonstrate that biomimetic geometries simulating budding robustly enhances fusion and alter spatial patterns of synthesis of pregnancy-related hormones. These findings indicate that biophysical signals play a previously unrecognized and significant role in regulating placental fusion and function, in synergy with established soluble signals. More broadly, our studies demonstrate that biomimetic strategies focusing on tissue mechanics can be important approaches to design, build, and test placental tissue cultures for future studies of pregnancy-related drug safety, efficacy and discovery.
Journal of Pineal Research, 2018
Melatonin has been proposed as a possible treatment for the deleterious effects of hypoxia/reoxyg... more Melatonin has been proposed as a possible treatment for the deleterious effects of hypoxia/reoxygenation (H/R), such as autophagy, inflammation, and apoptosis. Pathological pregnancies, such as preeclampsia, are associated with placental H/R, and decreased placental melatonin synthesis as well as lower melatonin levels in the placenta and maternal plasma. However, the effects of exogenous melatonin on inflammation and autophagy induced by pregnancy complications associated with H/R await investigation. This study aimed to determine as to whether melatonin protects human primary villous trophoblasts against H/R‐induced autophagy, inflammation, and apoptosis. Human primary villous cytotrophoblasts were isolated and immunopurified from normal term placentas. These cells were then exposed or not to 1 mmol/L melatonin for 72 hour in normoxia (8% O2), thereby inducing differentiation into syncytiotrophoblast that was then exposed to H/R (0.5% O2, for 4 hour) or normoxia. H/R decreased end...
Enfances, Familles, Générations
Cadre de la recherche : Bien que tous les résidents du Québec aient été affectés par la pandémie ... more Cadre de la recherche : Bien que tous les résidents du Québec aient été affectés par la pandémie de la COVID-19 et par les mesures sanitaires et sociales mises en place depuis le 13 mars 2020, les parents occupant un emploi rémunéré ont été particulièrement affectés par les différents stresseurs engendrés par cette crise, et ce, tant dans leur vie familiale que professionnelle. Dans un tel contexte, il apparaît pertinent de se pencher sur les conséquences engendrées par la pandémie sur la conciliation travail-famille, et plus particulièrement sur les facteurs qui y sont associés. Objectifs : La présente étude vise à documenter les caractéristiques personnelles, familiales et professionnelles associées à la conciliation travail-famille chez les employés universitaires ayant des enfants âgés de 11 ans ou moins dans le contexte de la pandémie. Méthodologie : Les données utilisées pour la présente étude ont été collectées entre le 24 avril et le 5 juin 2020 par le biais d’un sondage en ...
International Journal of Molecular Sciences
Bile acids (BAs) are natural ligands for several receptors modulating cell activities. BAs are sy... more Bile acids (BAs) are natural ligands for several receptors modulating cell activities. BAs are synthesized via the classic (neutral) and alternative (acidic) pathways. The classic pathway is initiated by CYP7A1/Cyp7a1, converting cholesterol to 7α-hydroxycholesterol, while the alternative pathway starts with hydroxylation of the cholesterol side chain, producing an oxysterol. In addition to originating from the liver, BAs are reported to be synthesized in the brain. We aimed at determining if the placenta potentially represents an extrahepatic source of BAs. Therefore, the mRNAs coding for selected enzymes involved in the hepatic BA synthesis machinery were screened in human term and CD1 mouse late gestation placentas from healthy pregnancies. Additionally, data from murine placenta and brain tissue were compared to determine whether the BA synthetic machinery is comparable in these organs. We found that CYP7A1, CYP46A1, and BAAT mRNAs are lacking in the human placenta, while corres...
Scientific Reports
Selective serotonin reuptake inhibitors (SSRIs) for treatment of prenatal maternal depression hav... more Selective serotonin reuptake inhibitors (SSRIs) for treatment of prenatal maternal depression have been associated with neonatal neurobehavioral disturbances, though the molecular mechanisms remain poorly understood. In utero exposure to SSRIs may affect DNA methylation (DNAme) in the human placenta, an epigenetic mark that is established during development and is associated with gene expression. Chorionic villus samples from 64 human placentas were profiled with the Illumina MethylationEPIC BeadChip; clinical assessments of maternal mood and SSRI treatment records were collected at multiple time points during pregnancy. Case distribution was 20 SSRI-exposed cases and 44 SSRI non-exposed cases. Maternal depression was defined using a mean maternal Hamilton Depression score > 8 to indicate symptomatic depressed mood (“maternally-depressed”), and we further classified cases into SSRI-exposed, maternally-depressed (n = 14); SSRI-exposed, not maternally-depressed (n = 6); SSRI non-e...
Human Molecular Genetics, 2021
Spontaneous preterm birth is a serious medical condition responsible for substantial perinatal mo... more Spontaneous preterm birth is a serious medical condition responsible for substantial perinatal morbidity and mortality. Its phenotypic characteristics, preterm labor with intact membranes (PTL) and preterm premature rupture of the membranes (PPROM), are associated with significantly increased risks of neurological and behavioral alterations in childhood and later life. Recognizing the inflammatory milieu associated with PTL and PPROM, here, we examined expression signatures of placental tryptophan metabolism, an important pathway in prenatal brain development and immunotolerance. The study was performed in a well-characterized clinical cohort of healthy term pregnancies (n = 39) and 167 preterm deliveries (PTL, n = 38 and PPROM, n = 129). Within the preterm group, we then investigated potential mechanistic links between differential placental tryptophan pathway expression, preterm birth and both intra-amniotic markers (such as amniotic fluid interleukin-6) and maternal inflammatory ...
Preeclampsia, 2017
Lack of blood flow and aberrant levels of oxygenation in placentas are recurrent in pregnancy dis... more Lack of blood flow and aberrant levels of oxygenation in placentas are recurrent in pregnancy diseases, such as preeclampsia. These alterations generate situations of hypoxia and hypoxia/reoxygenation (H/R) and consequent oxidative stress, increased cell death, and inflammation in trophoblasts. The models used to understand the effects of hypoxia and H/R on trophoblasts require a rather big structure. This chapter describes the details of a suitable and reasonable approach with hypoxia chambers to expose human placental trophoblasts to variable conditions of oxygenation.
Environmental Health Perspectives, 2019
Challenges, 2019
Work that addresses the cumulative impacts of resource extraction on environment, community, and ... more Work that addresses the cumulative impacts of resource extraction on environment, community, and health is necessarily large in scope. This paper presents experiences from initiating research at this intersection and explores implications for the ambitious, integrative agenda of planetary health. The purpose is to outline origins, design features, and preliminary insights from our intersectoral and international project, based in Canada and titled the “Environment, Community, Health Observatory” (ECHO) Network. With a clear emphasis on rural, remote, and Indigenous communities, environments, and health, the ECHO Network is designed to answer the question: How can an Environment, Community, Health Observatory Network support the integrative tools and processes required to improve understanding and response to the cumulative health impacts of resource development? The Network is informed by four regional cases across Canada where we employ a framework and an approach grounded in obser...
Connections for Health, Ecosystems and Society / The Fifth biennial conference of the Internation... more Connections for Health, Ecosystems and Society / The Fifth biennial conference of the International Association for Ecology and Health, August 11-15, Université du Québec à Montréal (Canada).
Journal of pineal research, 2015
Melatonin is highly produced in the placenta where it protects against molecular damage and cellu... more Melatonin is highly produced in the placenta where it protects against molecular damage and cellular dysfunction arising from hypoxia/re-oxygenation induced oxidative stress as observed in primary cultures of syncytiotrophoblast. However, little is known about melatonin and its receptor in the human placenta throughout pregnancy and their role in villous trophoblast development. The purpose of this study is to determine melatonin synthesizing enzymes; arylalkylamine N-acetyltransferase (AANAT) and hydroxyindole O-methyltransferase (HIOMT), and melatonin receptor (MT1 and MT2) expression throughout pregnancy as well as the role of melatonin and its receptors in villous trophoblast syncytialisation. Our data show that the melatonin generating system is expressed throughout pregnancy (from week 7 to term) in placental tissues. AANAT and HIOMT show maximal expression at the 3(rd) trimester of pregnancy. MT1 receptor expression is maximal at the 1(st) trimester compared to the 2(nd) and ...
Canadian journal of public health = Revue canadienne de santé publique, Jan 7, 2013
From a public health perspective, the follow-up of women during pregnancy and the perinatal perio... more From a public health perspective, the follow-up of women during pregnancy and the perinatal period requires quality communication and health services that take into account the context in which these women live. However, challenges related to access to health services in French in a minority situation have been documented in recent research. The objective of this pilot study is to better understand the perceptions, the lived experiences and the needs of pregnant Francophone women living in Canada within a linguistic minority context. Given the exploratory nature of the inquiry, a mixed method descriptive study was conducted in Alberta and New Brunswick, whose populations are 2% and 33% Francophone, respectively. Two semi-structured interviews and a series of validated questionnaires were administered to 21 pregnant women during the third trimester of pregnancy and at six weeks postnatal. Based on the questionnaires, a descriptive analysis documented participants' characteristics...
Reproductive BioMedicine Online, 2009
Dr Vaillancourt's main research goals are to elucidate the effect of environmental factors, such ... more Dr Vaillancourt's main research goals are to elucidate the effect of environmental factors, such as pollutants, depression and obstetric complications, on placental function and development. Her studies focus on placental dopaminergic, serotoninergic and melatoninergic systems.
Placenta, 2011
It is known that serotonin can influence the production and function of sex hormones, such as est... more It is known that serotonin can influence the production and function of sex hormones, such as estrogens. Estrogens are critical for maintenance of pregnancy and regulate placental and fetal development. The key enzyme controlling estrogens synthesis during pregnancy is placental aromatase (CYP19). To better understand the regulation of placental aromatase, this study determined whether serotonin is involved in the regulation of this enzyme. BeWo and JEG-3 choriocarcinoma cells were used as models of the human placental trophoblast to evaluate the effects of serotonin and selective 5-HT 2A receptor agonists on CYP19 activity and expression. Serotonin and selective 5-HT 2A receptor agonists as well as PKC activation increased aromatase activity and expression in BeWo and JEG-3 cells. Dexamethasone, which regulates aromatase expression via JAK/STAT activation in certain tissues, had no effect. Increased CYP19 gene transcription by 5-HT 2A receptor and PKC stimulation was mediated by activation of the placental I.1 aromatase promoter. This study shows that the serotonergic system modulates placental aromatase expression, which would result in altered estrogens biosynthesis in trophoblast cells. Future detailed studies of serotonineestrogen interactions in placenta are crucial for an improved understanding of the endo-, para-and autocrine role of serotonin during pregnancy and fetal development.
Placenta, 2011
Serotonin 5-HT 2A receptor activation improves viability, increases DNA synthesis and activates J... more Serotonin 5-HT 2A receptor activation improves viability, increases DNA synthesis and activates JAK2-STAT3 and MEK1/2-ERK1/2 signalling pathways in JEG-3 human trophoblast choriocarcinoma cells. The goal of this study was to characterize the signal transduction cascade involved in 5-HT 2A receptorinduced growth of JEG-3 cells. Selective 5-HT 2A receptor agonist, DOI, induced JEG-3 cell growth was inhibited by the inhibitor of JAK2 (AG490), MEK1/2 (U0126), phospholipase C-b (PLC-b; U73122) and protein kinase C-b (PKC-b; Gö6976)), whereas the selective phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002) had no effect. Specific inhibitors of PLC-b, PKC-b and Ras (farnesylthiosalicylic acid) inhibit activation of ERK1/2, whereas the PKC-z inhibitor GF109203X had no effect. Interestingly, inhibition of JAK2 prevented DOI-induced phosphorylation of ERK1/2 whereas inhibition of ERK1/2 pathway had no effect on DOI-induced activation of STAT3. Taken together, our results demonstrate that both the JAK2-STAT3 and PLC-b-PKC-bRas -ERK1/2 signalling pathways are involved in the stimulation of JEG-3 cell growth mediated by DOI. Moreover, this study shows that activation of JAK2 by the 5-HT 2A receptor is essential to activate both STAT3 and ERK1/2 signalling pathways as well as to increase JEG-3 choriocarcinoma cell growth and survival.
Molecular and Cellular Endocrinology, 2012
Melatonin has both the ability to induce intrinsic apoptosis in tumor cells while it inhibits it ... more Melatonin has both the ability to induce intrinsic apoptosis in tumor cells while it inhibits it in non-tumor cells. Melatonin kills tumor cells through induction of reactive oxygen species generation and activation of pro-apoptotic pathways. In contrast, melatonin promotes the survival of non-tumor cells due to its antioxidant properties and the inhibition of pro-apoptotic pathways. In primary human villous trophoblast, a known pseudo-tumorigenic tissue, melatonin promotes the survival through inhibition of the Bax/Bcl-2 pathway while in BeWo choriocarcinoma cell line melatonin induces permeabilization of the mitochondrial membrane leading to cellular death. These findings suggest that the trophoblast is a good model to study the differential effects of melatonin on the intrinsic apoptosis pathway. This review describes the differential effects of melatonin on the intrinsic apoptosis pathway in tumor and non-tumor cells and presents the trophoblast as a novel model system in which to study these effects of melatonin.
Molecular and Cellular Endocrinology, 2013