In the present review, we fi rst summarize the main benefi ts, 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 briefl y 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 fi rst 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 refi ned 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.

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