title: Adiponectin Inhibits Nutrient Transporters and Promotes Apoptosis in Human Villous Cytotrophoblasts: Involvement in the Control of Fetal Growth.
abstract: The placenta exchanges nutrients between the mother and the fetus and requires a constant abundant energy supply. Adiponectin (a cytokine produced primarily by adipose tissue) controls glucose and lipid homeostasis. It is well-known that maternal serum adiponectin levels are inversely related to birth weight, suggesting that adiponectin has a negative effect on fetal growth. This effect appears to be related to the control of nutrient transporters in human placenta. However, the underlying molecular mechanisms have not yet been characterized. In the present work, we studied adiponectin's direct effect on human primary cytotrophoblasts from first-trimester placenta. Our result showed that in placental cells, adiponectin 1) inhibits the expression of the major glucose transporters (GLUT1 and GLUT12) and sodium-coupled neutral amino acid transporters (SNAT1, SNAT2, and SNAT4), 2) enhances total ATP production but decreases lactate production, 3) inhibits mitochondrial biogenesis and function, and 4) stimulates cell death by enhancing the expression of the pro-apoptotic B-cell lymphoma-2 (BCL-2)-associated X protein (BAX) and tumor protein P53 (TP53) gene expression and inducing the caspase activity. Small-interfering RNA mediating the down-regulation of adiponectin receptors (ADIPOR1 and ADIPOR2) was used to demonstrate that adiponectin effects on placental nutrient transport and apoptosis seemed to be essentially mediated by these specific receptors. Taken as a whole, these results strongly suggest that adiponectin regulates human placental function by limiting nutrient transporter expression and inducing apoptosis. These findings may help us to better understand adiponectin's role in placental pathologies such as intrauterine growth restriction, which is characterized by fetal weight loss and drastic apoptosis of placental cells.
authors.affiliation: GIG-EA 7404, Université de Versailles-Saint Quentin en Yvelines, Unité de Formation et de Recherche des Sciences de la Santé Simone Veil, Montigny-le-Bretonneux, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Duval
authors.affiliation: GIG-EA 7404, Université de Versailles-Saint Quentin en Yvelines, Unité de Formation et de Recherche des Sciences de la Santé Simone Veil, Montigny-le-Bretonneux, France Service de Biologie Médicale, Centre Hospitalier de Poissy-Saint-Germain, Poissy, France.
authors.forename: Esther Dos
authors.initials: ED
authors.lastname: Santos
authors.affiliation: GIG-EA 7404, Université de Versailles-Saint Quentin en Yvelines, Unité de Formation et de Recherche des Sciences de la Santé Simone Veil, Montigny-le-Bretonneux, France.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Poidatz
authors.affiliation: GIG-EA 7404, Université de Versailles-Saint Quentin en Yvelines, Unité de Formation et de Recherche des Sciences de la Santé Simone Veil, Montigny-le-Bretonneux, France Service de Biologie Médicale, Centre Hospitalier de Poissy-Saint-Germain, Poissy, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Sérazin
authors.affiliation: GIG-EA 7404, Université de Versailles-Saint Quentin en Yvelines, Unité de Formation et de Recherche des Sciences de la Santé Simone Veil, Montigny-le-Bretonneux, France.
authors.forename: Héloïse
authors.initials: H
authors.lastname: Gronier
authors.affiliation: GIG-EA 7404, Université de Versailles-Saint Quentin en Yvelines, Unité de Formation et de Recherche des Sciences de la Santé Simone Veil, Montigny-le-Bretonneux, France Département de Biologie de la Reproduction, Cytogénétique, Gynécologie et Obstétrique, CHI de Poissy-Saint-Germain, Poissy, France.
authors.forename: François
authors.initials: F
authors.lastname: Vialard
authors.affiliation: GIG-EA 7404, Université de Versailles-Saint Quentin en Yvelines, Unité de Formation et de Recherche des Sciences de la Santé Simone Veil, Montigny-le-Bretonneux, France marie-noelle.dieudonne@uvsq.fr.
authors.forename: Marie-Noëlle
authors.initials: MN
authors.lastname: Dieudonné
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D002824:Chorionic Villi / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005317:Fetal Growth Retardation / Q000378:metabolism; D005502:Food; D051246:Glucose Transport Proteins, Facilitative / Q000037:antagonists & inhibitors; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D014327:Trophoblasts / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
chemical_list: D052242:Adiponectin; D051246:Glucose Transport Proteins, Facilitative; D026901:Membrane Transport Proteins
keywords: adiponectin; apoptosis; fetal growth; nutrient transporter; villous trophoblast