Integrative rodent models for assessing male reproductive toxicity of environmental endocrine active substances  

作　　者：Jacques Auger Florence Eustache Virginie Rouiller-Fabre Marie Chantal Canivenc-Lavier Gabriel Livera 

机构地区：[1]Service d'Histologie-Embryologie, Biologie de la Reproduction/CECOS, Site Port-Royal - Cochin/Broca/H6tel Dieu, H6pitaux Universitaires Paris Centre, Paris, France [2]Departement de Genetique et Developpement, INSERM U 567 and Institut Cochin, Universite Paris Descartes, Paris and Service d'Histologie-Embryologie-Cytogen6tique 8iologie de la Reproduction/CECOS, H6pital Jean Verdier, Bondy, France [3]1NRA/UMR 1324, CNRS/UMR6265, Centre des Sciences du GoOt et de I'Atimentation, Dijon, France. [4]Laboratoire de Developpement des Gonades, UMR 967 INSERM CEA DSV IRCM SCSR Universit Paris Diderot, Sorbonne Paris Cite Universit Paris Sud, Fontenay-aux Roses, France and

出　　处：《Asian Journal of Andrology》2014年第1期60-70,共11页亚洲男性学杂志（英文版）

摘　　要：In the present review, we first summarize the main benefits, limitations and pitfalls of conventional in vivo approaches to assessing male reproductive structures and functions in rodents in cases of endocrine active substance （EAS） exposure from the postulate that they may provide data that can be extrapolated to humans. Then, we briefly present some integrated approaches in rodents we have recently developed at the organism level. We particularly focus on the possible effects and modes of action （MOA） of these substances at low doses and in mixtures, real-life conditions and at the organ level, deciphering the precise effects and MOA on the fetal testis. It can be considered that the in vivo experimental EAS exposure of rodents remains the first choice for studies and is a necessary tool （together with the epidemiological approach） for understanding the reproductive effects and MOA of EASs, provided the pitfalls and limitations of the rodent models are known and considered. We also provide some evidence that classical rodent models may be refined for studying the multiple consequences of EAS exposure, not only on the reproductive axis but also on various hormonally regulated organs and tissues, among which several are implicated in the complex process of mammalian reproduction. Such models constitute an interesting way of approaching human exposure conditions. Finally, we show that organotypic culture models are powerful complementary tools, especially when focusing on the MOA. All these approaches have contributed in a combinatorial manner to a better understanding of the impact of EAS exposure on human reproduction.In the present review, we first summarize the main benefits, limitations and pitfalls of conventional in vivo approaches to assessing male reproductive structures and functions in rodents in cases of endocrine active substance （EAS） exposure from the postulate that they may provide data that can be extrapolated to humans. Then, we briefly present some integrated approaches in rodents we have recently developed at the organism level. We particularly focus on the possible effects and modes of action （MOA） of these substances at low doses and in mixtures, real-life conditions and at the organ level, deciphering the precise effects and MOA on the fetal testis. It can be considered that the in vivo experimental EAS exposure of rodents remains the first choice for studies and is a necessary tool （together with the epidemiological approach） for understanding the reproductive effects and MOA of EASs, provided the pitfalls and limitations of the rodent models are known and considered. We also provide some evidence that classical rodent models may be refined for studying the multiple consequences of EAS exposure, not only on the reproductive axis but also on various hormonally regulated organs and tissues, among which several are implicated in the complex process of mammalian reproduction. Such models constitute an interesting way of approaching human exposure conditions. Finally, we show that organotypic culture models are powerful complementary tools, especially when focusing on the MOA. All these approaches have contributed in a combinatorial manner to a better understanding of the impact of EAS exposure on human reproduction.

关 键 词：endocrine active substance endocrine disruptor exposure gonad in culture low dose mixture MOUSE rat RODENT strain 

分 类 号：Q959.837[生物学—动物学] S823.2[农业科学—畜牧学]