Maternal serotonin influences cardiac function in adult offspring.
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.
Fligny
Cécile
C
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.
Fromes
Yves
Y
Bonnin
Philippe
P
Darmon
Michèle
M
Bayard
Elisa
E
Launay
Jean-Marie
JM
Côté
Francine
F
Mallet
Jacques
J
Vodjdani
Guilan
G
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
D012701:Serotonin; C487801:Tph1 protein, mouse; D014365:Tryptophan Hydroxylase