title: Placental melatonin system is present throughout pregnancy and regulates villous trophoblast differentiation.
abstract: 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 receptors in the human placenta throughout pregnancy and their role in villous trophoblast development. The purpose of this study was to determine melatonin-synthesizing enzymes, arylalkylamine N-acetyltransferase (AANAT) and hydroxyindole O-methyltransferase (HIOMT), and melatonin receptors (MT1 and MT2) expression throughout pregnancy as well as the role of melatonin and its receptors in villous trophoblast syncytialization. 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 3rd trimester of pregnancy. MT1 receptor expression is maximal at the 1st trimester compared to the 2nd and 3rd trimesters, while MT2 receptor expression does not change significantly during pregnancy. Moreover, during primary villous cytotrophoblast syncytialization, MT1 receptor expression increases, while MT2 receptor expression decreases. Treatment of primary villous cytotrophoblast with an increasing concentration of melatonin (10 pM-1 mM) increases the fusion index (syncytium formation; 21% augmentation at 1 mM melatonin vs. vehicle) and β-hCG secretion (121% augmentation at 1 mM melatonin vs. vehicle). This effect of melatonin appears to be mediated via its MT1 and MT2 receptors. In sum, melatonin machinery (synthetizing enzymes and receptors) is expressed in human placenta throughout pregnancy and promotes syncytium formation, suggesting an essential role of this indolamine in placental function and pregnancy well-being.
authors.affiliation: INRS-Institut Armand-Frappier and BioMed research Center, Université du Québec, Laval, QC, Canada.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Soliman
authors.affiliation: INRS-Institut Armand-Frappier and BioMed research Center, Université du Québec, Laval, QC, Canada.
authors.forename: Andrée-Anne
authors.initials: AA
authors.lastname: Lacasse
authors.affiliation: INRS-Institut Armand-Frappier and BioMed research Center, Université du Québec, Laval, QC, Canada.
authors.forename: Dave
authors.initials: D
authors.lastname: Lanoix
authors.affiliation: INRS-Institut Armand-Frappier and BioMed research Center, Université du Québec, Laval, QC, Canada.
authors.forename: Lucas
authors.initials: L
authors.lastname: Sagrillo-Fagundes
authors.affiliation: INRS-Institut Armand-Frappier and BioMed research Center, Université du Québec, Laval, QC, Canada.
authors.forename: Véronique
authors.initials: V
authors.lastname: Boulard
authors.affiliation: INRS-Institut Armand-Frappier and BioMed research Center, Université du Québec, Laval, QC, Canada.
authors.forename: Cathy
authors.initials: C
authors.lastname: Vaillancourt
mesh_terms: D000121:Acetylserotonin O-Methyltransferase / Q000235:genetics / Q000378:metabolism; D047068:Arylalkylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002824:Chorionic Villi / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008550:Melatonin / Q000494:pharmacology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D044122:Receptor, Melatonin, MT1 / Q000235:genetics / Q000378:metabolism; D044123:Receptor, Melatonin, MT2 / Q000235:genetics / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D000121:Acetylserotonin O-Methyltransferase; C478879:AANAT protein, human; D047068:Arylalkylamine N-Acetyltransferase; D008550:Melatonin
keywords: HIOMT (ASMT); MT1 melatonin receptor; MT2 melatonin receptor; arylalkylamine N-acetyltransferase; human chorionic gonadotropin; syncytiotrophoblast; villous cytotrophoblast