Endocrine Abstracts

Many industrial chemicals and pharmaceutical products have been proposed to result in endocrine disruption in humans. This includes potential effects on reproductive development in males and females. Chemicals that have been proposed to impact on male reproductive development include plasticizers, synthetic oestrogens and analgesics. Much of the data on the effect of exposure to these agents are based on studies conducted in rodent models; however, confirmation of such findings in human model systems at human-relevant exposure levels are lacking.

We have developed model systems to determine the effects of exposure to a variety of proposed ‘EDCs’ on human fetal testis development and function. Using a xenograft system designed to reproduce normal fetal testis development and in-utero hormonal environment, our results demonstrate important species differences in the effects of exposure to chemicals such as di-n-butyl phthalate (DBP) and diethylstilboestrol (DES) in terms of testosterone production. We have also demonstrated that exposure to analgesics, such as paracetamol, result in a significant reduction in testosterone production and also impact on germ cell development in the human fetal testis. Importantly, these effects are apparent at therapeutic levels of exposure using a standard therapeutic regimen.

Our work, in addition to that of several other groups, highlight the importance of choosing an appropriate model species, experimental system and relevant exposure regimen in order to determine the potential impact of EDC exposure in humans. Findings from rodent studies should, where possible, be confirmed using human tissue models in order to determine the relevance to human health.