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• W2021303500 abstract "P-242 Abstract: “Endocrine disrupters” have become a growing concern as a public health issue. The hypothesis that hormonally active compounds in the environment are having a significant impact on human and ecological health has captured the public attention like no other toxicity since the publication of Rachel Carson's Silent Spring in 1962 and the increase in hormone-dependant pathology such as cancer in both male and female in target tissues as well as the incidence of developmental defects such as hypospadias and cryptorchidism and the decline of semen quality in men. A number of different in vivo and in vitro assays have already been used to identify many compounds, but it has been recognised that there is an urgent need to establish screening tests to identify and classify the endocrine potential of these EDCs. Thus we have conducted a study in order to develop a relevant test method, based on observations from literature, considering advantages and drawbacks of the current screening tests. We will propose an in vivo model of EDCs exposure: the Aromatse-KO mouse model. The gene targeted-disruption abolishes the whole expression of the cytochrome P450 enzymatic complex, belonging to the superfamily of CYP19 proteins, involved in the bioconversion of androgens into estrogens. The main advantage of this transgenic model is to be free of endogenous estrogens but still sensitive to estrogenic compounds as well as anti/androgenic compounds. This model has been exposed to 3 doses of either methoxychlor or vinclozolin at adult age and in utero (from GD14 to GD19), and the variation of expression of genes of the steroidogenic pathway (AR, ER alpha/ ER beta, PR) and genes involved in the sex determination and differentiation (SOX9, AMH) have been studied using the real time RT-PCR method with the SYBR Green I as the fluorescent format. Histological studies have also been conducted on ovaries and testis of both adults and in utero groups. Both genomic and histological studies demonstrate the defects of such compounds acting on the steroidogenic enzymes. To conclude this model allowed us to improve the knowledge of the normal physiology and the effects of compounds that can have both estrogenic and anti/androgenic compounds. ArKO and ERKO mouse models provide the long-awaited tools necessary to overcome obstacles encountered in endocrinology and toxicology studies. They continue to illustrate the numerous ways in which the generation and study of KO models can quickly contribute to the knowledge concerning EDCs compounds." @default.
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• W2021303500 date "2006-11-01" @default.
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• W2021303500 title "A New In Vivo Model to Screen Both Estrogenic and Anti-/Androgenic Compounds" @default.
• W2021303500 doi "https://doi.org/10.1097/00001648-200611001-00879" @default.
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