Immunomodulation by maternal autoantibodies of the fetal serotoninergic 5-HT4 receptor and its consequences in early BALB/c mouse embryonic development.
2007
Kamel, Rehab | Garcia, Simone | Lezoualc'H, Frank | Fischmeister, Rodolphe | Muller, Sylviane | Hoebek, Johan | Eftekhari, Pierre | Laboratoire de tectonique (LT) ; Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Cergy Pontoise (UCP) ; Université Paris-Seine-Université Paris-Seine-Centre National de la Recherche Scientifique (CNRS) | Neurosciences Sensorielles Comportement Cognition ; Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS) | Signalisation et physiopathologie cardiaque ; Université Paris-Sud - Paris 11 (UP11)-IFR141-Institut National de la Santé et de la Recherche Médicale (INSERM) | Innovation Thérapeutique : du Fondamental au Médicament ; Institut National de la Recherche Agronomique (INRA)-Université Paris-Sud - Paris 11 (UP11)-MEDICEN-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) | Institut de RadioAstronomie Millimétrique (IRAM) ; Centre National de la Recherche Scientifique (CNRS) | Academia Sinica Institute of Astronomy and Astrophysics (ASIAA) ; Academia Sinica | Laboratoire Biodiversité et Fonctionnement des Ecosystèmes (LBFE) ; Université Paul Verlaine - Metz (UPVM) | Immunologie et chimie thérapeutiques (ICT) ; Institut de biologie moléculaire et cellulaire (IBMC) ; Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS) | Institut de biologie moléculaire et cellulaire (IBMC) ; Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS) | Laboratoire de Chimie et Applications (LCA) ; Université Paul Verlaine - Metz (UPVM)
BACKGROUND: The presence of functional 5-HT4 receptors in human and its involvement in neonatal lupus erythematosus (NLE) have prompted us to study the receptor expression and role during embryogenesis. Earlier we managed to demonstrate that female BALB/c mice immunized against the second extracellular loop (SEL) of the 5-HT4 receptor gave birth to pups with heart block. To explain this phenomenon we investigated the expression of 5-HT4 receptors during mouse embryogenesis. At the same time we looked whether the consequence of 5-HT4 receptor immunomodulation observed earlier is in relation to receptor expression.We studied the expression of 5-HT4 receptor at the mRNA level and its two isoforms 5-HT4(a) and 5-HT4(d) at the protein level in embryos from BALB/c mice, at 8th, 12th, 18th gestation days (GD) and 1 day post natal (DPN). Simultaneously the receptor activity was inhibited by rising antibodies, in female mice against SEL of the receptor. The mice were mated and embryos were collected at 8th, 12th, 18th GD and 1 DPN. RESULTS: 5-HT4 receptor mRNA increased in brain from 12th GD to 1 DPN. Its expression gradually decreased in heart and disappeared at birth. This was consistent with expression of the receptor isoforms 5-HT4(a) and (d). Abnormalities like decreased number of embryos, growth delay, spina bifida and sinus arrhythmia from 12th GD were documented in pups of mice showing anti-5-HT4 receptor antibodies. CONCLUSION: serotoninergic 5-HT4 receptor plays an important role in mouse foetal development. In BALB/c mice there is a direct relation between the expression of receptor and the deleterious effect of maternal anti-5-HT4 receptor autoantibodies in early embryogenesis.
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