Endocrine disruption and steroidogenesis : integrated evaluation from gonadal steroidogenic enzymes in vitro and in vivo to hormonal balance and fertility assessment in vivo
Résumé
In the present study, we propose an integrated evaluation of the effects of some endocrine disruptors in vivo in male and female adult rats, and in vitro in several models. We focused our work on the last step of steroidogenesis and the aim was to determine to what extent in vitro models could be predictive of in vivo alterations. We have evaluated the selected chemicals for their ability to modulate the expression and activity of steroidogenic enzymes in vitro and in vivo, to disrupt hormonal balance, and to disrupt certain fertility parameters, during a sub-acute exposure. Gene expression profiles were assessed by RT-qPCR, in vitro and ex vivo aromatase activity was assessed by the method of tritiated water, blood and gonadal steroid concentrations were evaluated with LC-MS/MS and ELISA. Our results showed that all treatments induced disturbance of hormonal balance, which was related to gene expression disordersin some cases. For example, rats treated with atrazine presented high levels of estradiol and low levels of testosterone. This observation may be related to aromatase induction observed in testes and ovaries as well as in gonadal primary cultures and cell lines. A decrease of testosterone level is also observed in male rats treated with methoxychlor, which can be linked not only to aromatase induction, but also to HSD17B3down-regulation.Taken together, these results contribute to identify toxic endpoints as well as relevant biomarkers of endocrine disruption. Further studies should determine if, on the basis of these data, anew predictive tool could be developed for endocrine disrupting chemicals assessment.