title: Maternal serotonin influences cardiac function in adult offspring.
abstract: Using the Tph1-invalidated mouse line, in which blood is depleted in serotonin (5-hydroxytryptamine, 5-HT), we have demonstrated previously that maternal 5-HT is required for normal embryonic development. Here, we address the issue of the influence of the maternal 5-HT concentration on the cardiac function of the offspring as adults. We investigated the cardiac phenotype of Tph1-invalidated mice born to Tph1 heterozygous and null mothers. Functionally, all mutants display a significant decrease of cardiac contractility, indicative of impaired left ventricular function. They exhibit progressive dilated cardiomyopathy and are unable to adapt appropriately to a pharmacological stress. Moreover, we show that the cardiopathy is more severe in adult Tph1(-/-) mice born to homozygous mothers than to heterozygous mothers. Importantly, the severity of the cardiac phenotype is inversely correlated with the plasma 5-HT concentration but not the whole-blood 5-HT concentration. Thus, plasma 5-HT concentration may be a useful index of heart failure. These findings show that cardiac function, through the plasma 5-HT concentration, is influenced by the maternal serotonergic status.
authors.affiliation: Unité Mixte de Recherche 7091 Centre National de la Recherche Scientifique/Université Pierre et Marie Curie, Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, Hôpital de la Pitié-Salpêtrière, Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Fligny
authors.forename: Yves
authors.initials: Y
authors.lastname: Fromes
authors.forename: Philippe
authors.initials: P
authors.lastname: Bonnin
authors.forename: Michèle
authors.initials: M
authors.lastname: Darmon
authors.forename: Elisa
authors.initials: E
authors.lastname: Bayard
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Launay
authors.forename: Francine
authors.initials: F
authors.lastname: Côté
authors.forename: Jacques
authors.initials: J
authors.lastname: Mallet
authors.forename: Guilan
authors.initials: G
authors.lastname: Vodjdani
mesh_terms: D000818:Animals; D004562:Electrocardiography; D047108:Embryonic Development / Q000502:physiology*; D005260:Female; D006580:Genetic Carrier Screening; D006321:Heart / Q000502:physiology*; D006334:Heart Function Tests; D006720:Homozygote; D051379:Mice; D018345:Mice, Knockout; D012701:Serotonin / Q000502:physiology*; D015398:Signal Transduction; D014365:Tryptophan Hydroxylase / Q000172:deficiency / Q000235:genetics / Q000502:physiology
chemical_list: D012701:Serotonin; C487801:Tph1 protein, mouse; D014365:Tryptophan Hydroxylase