6533b7d3fe1ef96bd125fd3c

RESEARCH PRODUCT

Actions différentielles de xéno-hormones alimentaires sur les organes reproducteurs, le foie et le tissu adipeux chez le rat femelle : aspects endocriniens, métaboliques et morphogénétiques en relation avec les processus de cancérogenèse

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Differential actions of dietary xenohormones on the reproductive organs, the liver and the adipose tissue in the female rat : endocrine, metabolic and morphogenetic aspects regarding the carcinogenic process. Over the past décades, the incidence of hormone-dependent cancers has dramatically increased in Western countries as compared to Asian countries. Environmental and dietary compounds able to mimic and interfère with endogenous hormones, especially reproductive ones, may be involved and among these xenohormones. xenoestrogens (XE) are particularly pointed at. The objective of this thesis was to détermine the conséquences of chronic dietary exposure to phytoestrogens and chemical xenoestrogens on female reproductive organs and on tissues involved in the carcinogenic process, at key development stages. Based on human developmental stage-spécifie diet, severa] expérimental models in the female rat were used to characîerize xenoestrogen-induced endocrine, metabolic and morphogenetic changes. Our results show that target organs like reproductive organs and mammary gland are particularly sensitive during the ménopausal and the périnatal periods. Exposure to multiple XE during aduîthood caused modulation of hepatic oxidative metabolism of estradiol towards potentially genotoxic derivatives and highlighted complex interactions between xenoestrogens, endogenous estrogens and 7,12-dimethylbenz(a)anthracene, a chemical caremogen. Besides, XE were able to target adipose tissue and the adipogenic process : taking into account the rôle of adipose tissue in cancer development, questions arise from XE-induced functional alterations in ternis of carcinogenic outeomes. In conclusion, this work emphasizes the complex and pleiotropic action of xenohormones and highlights several mechanisms by which they can impact the carcinogenic process at différent development stages.