LA CONTRACEPTION A TRAVERS LES AGES, EVOLUTION ET INFLUENCE DES FACTEURS SOCIOLOGIQUES

NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Quelle première contraception orale estroprogestative chez la femme de moins de 35 ans

En 1992 quatre millions de femmes utilisaient une contraception orale. Celle ci est un motif fréquent de consultation chez le médecin généraliste qui doit choisir parmi une grande panoplie de pilules. Nous avons réalisé une revue de la littérature pour aborder la question quelle contraception orale estroprogestative choisir en première intention chez la femme de moins de 35 ans sans contre-indication. Le premier contraceptif oral estroprogestatif a été disponible en France en 1961, depuis la panoplie thérapeutique s'est agrandie. Nous avons examiné les articles parus sur l'efficacité contraceptive, les risques cardiovasculaires ( comprenant les thromboses veineuses profondes, l'infarctus aigu du myocarde, les accidents cérébrovasculaires ), le risque de cancer et la tolérance clinique . Nous avons retrouvé peu d'études et celles recensées n'étaient le plus souvent que d'un niveau de preuve 2. Afin d'aboutir à un grade de recommandation A basé sur un niveau de preuve 1 il faut réaliser d'autres études sur les effets des différents dosages en éthinylestradiol et les différents progestatifs des contraceptifs oraux estroprogestatifs.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Sex-specific transgenerational effects on murine thyroid gland imposed by ancestral exposure to neonicotinoid thiacloprid

International audienceNeonicotinoids, a relatively new widely used class of insecticide is used in agriculture to control insect populations. We examined the capacity of ancestral exposure to the neonicotinoid thiacloprid (thia) to induce transgenerational effects on thyroid tissue. Pregnant outbred Swiss female mice were exposed to thia at embryonic days E6.5 to E15.5 using 0, 0.6, and 6 mg/kg/day doses. Thyroid paraffin sections were prepared for morphology analysis. We apply ELISA method to measure T4 and TSH levels, RT-qPCR for gene expression analysis, ChIP-qPCR techniques for sperm histone H3K4me3 analysis, and immunofluorescence microscopy and western blots for protein detection. We observed an alteration in the morphology of thyroids in both males and females in the F3 generation. We observed an increase in T4 hormone in F1 females and a significant T4 level decrease in F3 males. T4 changes in F1 females were associated with a TSH increase. We found that the amount of Iodothyronine Deiodinase 1 (DIO1) (an enzyme converting T4 to T3) was decreased in both F1 and F3 generations in female thyroids. GNAS protein which is important for thyroid function has increased in female thyroids. Gene expression analysis showed that the expression of genes encoding thyroid gland development, chromatin, biosynthesis and transport factors were affected in the thyroid gland in both sexes in F1 and F3. The analysis of sperm histone H3K4me3 showed that H3K4me3 occupancy at the Dio1 locus has decreased while Thyroglobulin (Tg) and Matrix Metallopeptidase 2 (Mmp2) genes have increased H3K4me3 occupancy in the sperm of F3 mice. Besides, DNA methylation analysis of our previously published datasets showed that, in the sperm of F1 and F3 thia-derived mice, several genes related to thyroid function show consistent alterations. Our data suggest that ancestral exposure to thiacloprid affects thyroid function not only in exposed but also in indirectly exposed F3 generation