title: Serotonin transporter protects the placental cells against apoptosis in caspase 3-independent pathway.
abstract: Serotonin (5-HT) and its specific transporter, SERT play important roles in pregnancy. Using placentas dissected from 18d gestational SERT-knock out (KO), peripheral 5-HT (TPH1)-KO, and wild-type (WT) mice, we explored the role of 5-HT and SERT in placental functions in detail. An abnormal thick band of fibrosis and necrosis under the giant cell layer in SERT-KO placentas appeared only moderately in TPH1-KO and minimally present in WT placentas. The majority of the changes were located at the junctional zone of the placentas in SERT. The etiology of these findings was tested with TUNEL assays. The placentas from SERT-KO and TPH1-KO showed 49- and 8-fold increase in TUNEL-positive cells without a concurrent change in the DNA repair or cell proliferation compared to WT placentas. While the proliferation rate in the embryos of TPH1-KO mice was 16-fold lower than the rate in gestational age matched embryos of WT or SERT-KO mice. These findings highlight an important role of continuous 5-HT signaling on trophoblast cell viability. SERT may contribute to protecting trophoblast cells against cell death via terminating the 5-HT signaling which changes cell death ratio in trophoblast as well as proliferation rate in embryos. However, the cell death in SERT-KO placentas is in caspase 3-independent pathway.
authors.affiliation: Departments of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, Arkansas.
authors.forename: Coedy
authors.initials: C
authors.lastname: Hadden
authors.affiliation: Department of Pharmacology, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, Arkansas.
authors.forename: Tariq
authors.initials: T
authors.lastname: Fahmi
authors.affiliation: Departments of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, Arkansas.
authors.forename: Anthonya
authors.initials: A
authors.lastname: Cooper
authors.affiliation: Department of Pharmacology, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, Arkansas.
authors.forename: Alena V
authors.initials: AV
authors.lastname: Savenka
authors.affiliation: Department of Physiology College of Medicine, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, Arkansas.
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Lupashin
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Drucilla J
authors.initials: DJ
authors.lastname: Roberts
authors.affiliation: Institut du Fer a' Moulin, UMR-S839 INSERM, Université Pierre et Marie Curie, Paris, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Maroteaux
authors.affiliation: Reproductive Biology, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Hauguel-de Mouzon
authors.affiliation: Departments of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, Arkansas.
authors.forename: Fusun
authors.identifier: http://orcid.org/0000-0003-3408-5543
authors.initials: F
authors.lastname: Kilic
mesh_terms: D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism*; D049109:Cell Proliferation; D005260:Female; D005838:Genotype; D007328:Insulin / Q000097:blood; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D010920:Placenta / Q000201:enzymology* / Q000378:metabolism; D011247:Pregnancy; D012701:Serotonin / Q000097:blood / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D012701:Serotonin; C487801:Tph1 protein, mouse; D014365:Tryptophan Hydroxylase; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: placenta; serotonin; serotonin transporter