Maternal and Fetal Exposure to Bisphenol A Is Associated with Alterations of Thyroid Function in Pregnant Ewes and Their Newborn Lambs

The putative thyroid-disrupting properties of bisphenol A (BPA) highlight the need for an evaluation of fetal exposure and its consequence on the mother/newborn thyroid functions in models relevant to human. The goals of this study were to characterize in sheep a relevant model for human pregnancy and thyroid physiology, the internal exposures of the fetuses and their mothers to BPA and its main metabolite BPA-glucuronide (Gluc), and to determine to what extent it might be associated with thyroid disruption. Ewes were treated with BPA [5 mg/(kg . d) sc] or vehicle from d 28 until the end of pregnancy. Unconjugated BPA did not appear to accumulate in pregnant ewes, and its concentration was similar in the newborns and their mothers (0.13 +/- 0.02 and 0.18 +/- 0.03 nmol/ml in cord and maternal blood, respectively). In amniotic fluid and cord blood, BPA-Gluc concentrations were about 1300-fold higher than those of BPA. Total T-4 concentrations were decreased in BPA-treated pregnant ewes and in the cord and the jugular blood of their newborns (30% decrease). A similar difference was observed for free T-4 plasma concentrations in the jugular blood of the newborns. Our results show in a long-gestation species with a similar regulatory scheme of thyroid function as humans that BPA in utero exposure can be associated with hypothyroidism in the newborns. If such an effect were to be confirmed for a more relevant exposure scheme to BPA, this would constitute a major issue for BPA risk assessment

Inflammatory control in AIDS-resistant non human primates

International audienceAfrican non human primates are natural hosts of SIV. The infection is non-pathogenic despite plasma viral load levels similar to those in HIV-1 infected humans and SIVmac-infected macaques (MAC) progressing towards AIDS. The most striking difference between non-pathogenic SIV and pathogenic HIV-1/SIVmac infections is the lack of chronic T cell activation in natural hosts. In HIV and SIVmac infections, chronic T cell activation is known to drive CD4+T cell depletion. Intense research efforts are worldwide put on the search of the mechanisms that can control chronic T cell activation in HIV/SIV infections. Innate immune responses play a determinant role in the regulation of T cell activation profiles. Type I interferons (IFN-I) are part of the first-wave response of the innate immune system in viral infections. We compared the IFN-I responses between pathogenic (MAC) and non-pathogenic SIV infections (African Green monkey, AGM) at the level of blood and lymph nodes (LN) during the early and chronic stage of infection. During the acute SIVagm infection, we detected high amounts of IFN-α in the plasma of AGMs, although the mean levels at the peak were three times lower than in MAC. The microarray data revealed a rapid and strong up-regulation of type I Interferon-Stimulated Genes (ISG) in AGMs during acute SIVagm infection. ISGs denote the in vivo activity of IFN-I. Using a functional assay, we demonstrated that low IFN-α concentrations (50 times lower than the IFN-α levels in plasma at the peak) were sufficient to induce strong ISG responses in AGM and MAC cells. Surprisingly, our direct comparison of blood and LNs showed that ISG induction was broader in blood of AGMs than in MAC, while in LN, it was the contrary. Thus, in AGMs, less ISG were induced in LNs as compared to MAC already during the acute phase of infection. Moreover, our tight kinetic analysis showed that this ISG expression was efficiently controlled after day 28 post-infection in AGMs, while in MAC the ISGs expression remained uncontrolled. Finally, we identified genes that were differentially expressed between the two species and which might be involved in the discriminating responses. Altogether, this shows that AGMs are capable to mount a well coordinated and efficient regulative response to innate immune activation

Bases mécanistiques des effets d'un insecticide agrovétérinaire, le fipronil,et/ou de ses métabolites sur la fonction thyroîdienne chez le rat

Le fipronil, insecticide largement utilisé, est un perturbateur thyroïdien chez le rat modulant le catabolisme hépatique des hormones thyroïdiennes. Ses effets chez le mouton, considéré comme un modèle plus pertinent que le rat pour étudier une régulation de la fonction thyroïdienne chez l'Homme, sont plus limités. Le but de cette thèse était de caractériser au niveau hépatique le mode d'action du fipronil sur la fonction thyroïdienne en s'intéressant 1) au rôle potentiel du principal métabolite du fipronil formé in vivo, le fipronil sulfone, et 2) aux différences interspécifiques de métabolisme du fipronil et/ou de sensibilité à la perturbation thyroïdienne qui peuvent préjuger de la pertinence des différents modèles animaux pour l'analyse du risque du fipronil pour la santé humaine. L'efficacité du fipronil sulfone à induire l'expression et/ou l'activité d'enzymes responsables du métabolisme hépatique des hormones thyroïdiennes ou du fipronil était la même que celle du fipronil autant in vivo chez le rat que in vitro sur hépatocytes. L'utilisation d'un modèle de souris déficientes pour des récepteurs nucléaires xénosenseurs suggérait fortement une implication des récepteurs nucléaires Constitutive Androstane Receptor et/ou Pregnane X Receptor dans la perturbation thyroïdienne induite par le fipronil

Médicaments psychotropes et grossesse (enquête auprès de 150 femmes enceintes dans le service des grossesses pathologiques de Purpan)

TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

LE FILS PRODIGUE ET LES SIENS (XX E -XXI E SIECLES) : AMOUR, VIOLENCE ET PERVERSION

International audienc

LE FILS PRODIGUE ET LES SIENS (XX E -XXI E SIECLES) : AMOUR, VIOLENCE ET PERVERSION

International audienc

Développement d'une nouvelle méthode de dosage des hormones thyroïdiennes (T3 et T4) et metabolites par UHPLC MS/MS

Notre objectif a été de développer et optimiser une nouvelle méthode de dosage de la T3, de la T4 et de 6 de leurs métabolites

Le metabarcoding pour la détection et l’identification d’insectes invasifs

International audienc