The objectives of this study were to determine: the effects of maternal melatonin (MEL) supplementation during late gestation on the histological and molecular regulation in the Longissimus dorsi (LM) muscle of fetal bovine offspring, composition and gene expression of fetal perirenal (PR) adipose tissue, and LM gene expression in postnatal offspring at birth and d 195 of age. Maternal supplementation of MEL during late gestation resulted in no difference in calf fetal body weight or birth weight. However, at d 195 of age, calves from MEL treated dams had an average body weight increase of 20 kg. Fetal LM weight and length tended to be increased in calves from MEL treated dams. Fetal gene expression of calves from MEL treated dams resulted in: increased LM adenosine monophosphate-activated protein kinase-α (AMPK) and decreased PR adiponectin (ADIPOQ), CCAAT enhancer binding protein alpha (CEBPA), proliferator activated receptor gamma (PPARg), and stearoyl-CoA desaturase (SCD). The improved metabolic status of LM coupled with the decrease in adipogenic gene expression, could result in calves from MEL treated dams having improved lean muscle accretion and reduced overall adiposity during postnatal development.

L'exposition durant la vie périnatale à des perturbateurs endocriniens (PE) anti-androgéniques, induit des altérations durables du système reproducteur mâle. Si leur action a été objectivée chez l’homme et l’animal, la question du seuil de toxicité reste entière, car l’exposition environnementale correspond à de faibles doses. Ici, nous exposons in utero des rats mâles à de faibles doses de flutamide: 10 mg/kg/j ; 1; 3 doses faibles selon la définition de l'OMS 0.1; 0.01; 0.001 et 0. L'exposition fœtale induit chez l’adulte (1) des altérations morphologiques à la dose 10 mg/kg/j (diminution du poids des organes du tractus génital et une diminution du compte spermatique); (2) des altérations cellulaires à partir de 1mg (augmentation de l'apoptose des cellules germinales) et (3) des altérations moléculaires à toutes les doses testées pour MCL1, BCL2, XIAP, HSPA2, ELAVL1 et MOV10L1. Ces altérations s’intègrent dans la dérégulation de 2 voies de signalisation expliquant l’apoptose des cellules germinalesLorsque l’exposition a lieu à l’âge l’adulte dans les mêmes conditions, les effets morphologiques et cellulaires sont observés uniquement à 10mg, les effets moléculaires uniquement aux doses 10 et 1 mg. Ces effets ne sont plus observés 2 mois après l’arrêt de l’exposition. En conclusion : Nous avons (i) identifié des voies de signalisation impliquées dans le phénotype d’infertilité induite par une exposition à de faibles doses d’anti-androgène ; (ii) montré que ces voies étaient actives aux plus faibles doses testées prédisposant à une infertilité masculine programmée in utero / Exposure during perinatal life to anti-androgenic endocrine disruptors (ED) induces sustained alterations of the male reproductive system. Although their action has been objectified in humans and animals, the question of the threshold of toxicity remains unchanged, as environmental exposure corresponds to low doses. Here, we exposed male rats, in utero, to low doses of flutamide: 10 mg/kg/d; 1; 3 low doses as defined by WHO 0.1; 0.01; 0.001 and 0. Fetal exposure induced in adults (1) morphological alterations at a dose of 10 mg/kg/day (decrease in the weight of organs of the genital tract and a decrease in the sperm count); (2) cellular alterations from 1mg (increase in germ cell apoptosis) and (3) molecular alterations at all doses tested for MCL1, BCL2, XIAP, HSPA2,LAVL1 and MOV10L1. These alterations are integrated in the deregulation of 2 signaling pathways explaining the apoptosis of the germ cellsWhen exposure occurs at adult age under the same conditions, morphological and cellular effects are observed only at 10mg, molecular effects only at doses 10 and 1 mg. These effects are no longer observed 2 months after discontinuation of exposure. In conclusion: We have (i) identified signaling pathways involved in the phenotype of infertility induced by exposure to low doses of antiandrogen; (ii) showed that these pathways were active at the lowest doses tested predisposing to programmed male infertility in utero