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

• Published in: Asian journal of andrology 2014-01, Vol.16 (1), p.60-70
• Main Authors: Auger, Jacques, Eustache, Florence, Rouiller-Fabre, Virginie, Canivenc-Lavier, MarieChantal, Livera, Gabriel
• Format: Article
• Language: English
• Subjects: Animals; Biodiversity and Ecology; endocrine active substance; endocrine disruptor; exposure; gonad in culture; low dose; mixture; mouse; rat; rodent; strain; Endocrine Disruptors - toxicity; Environmental Exposure - adverse effects; Environmental Sciences; Experiments; Fetus; Humans; Invited Review; Life Sciences; Male; Metabolism; Models, Animal; Organ Culture Techniques; Organisms; Oxazoles - toxicity; Physiology; Reproduction - drug effects; Reproductive Biology; Reproductive system; Rodents; Sexual reproduction; Spermatozoa - drug effects; Testis - drug effects; Testis - embryology; Toxicity; 内分泌; 动物模型; 啮齿类动物; 活性物质; 生殖毒性; 评估; 金属氧化物避雷器; 雄性
• ISSN: 1008-682X; 1745-7262
• DOI: 10.4103/1008-682X.122366

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.