Endocrine Abstracts

Context: In rodents, in-utero exposure to the exogenous oestrogen diethylstilboestrol (DES) results in reproductive abnormalities in male offspring. It has been proposed that similar anti-androgenic effects also occur in the human fetal testis following oestrogen exposure.

Objective: Determine effects of DES exposure on testosterone production by normally growing human fetal testis xenografts.

Design: Human fetal testes (15–19 weeks gestation, n=6) were xenografted into castrate male nude mice. Mice were treated for 35 days with vehicle or 100 μg/kg DES three times a week; all mice were treated with hCG to mimic normal human pregnancy. For comparison, fetal male rats were exposed in-utero to vehicle or 100 μg/kg DES on e13.5, e15.5, e17.5, e19.5 and e20.5.

Main outcome measures: Testosterone production from xenografts was assessed by measuring host serum testosterone and seminal vesicle (SV) weights at termination. Insl3 production was determined in serum, whilst immunohistochemistry was performed for Insl3 and ERα.

Results: Human fetal testis xenografts showed similar survival and total graft weight in DES and vehicle-exposed hosts. SV weight was significantly increased in DES compared to vehicle-exposed hosts (44.3 vs 26.6 mg, P=0.01) and testosterone was also increased (0.33 vs 0.45 ng/ml, P>0.05). There was no difference in Insl3 expression. In contrast, in-utero exposure of fetal rats to DES resulted in significantly lower intra-testicular testosterone levels associated with a reduction in Insl3 expression. ERα was expressed in fetal rat testis but was not expressed in the human fetal testis.

Conclusions: Exposure of human fetal testes to DES does not impair testosterone production as it does in rats. This can be explained by a lack of ERα signalling in the human fetal testis. This highlights an important difference in the effect of proposed ‘endocrine disruptors’ in humans compared with rodents which has important implications for determining the risk posed to human health by environmental oestrogens.

Declaration of funding: This work was supported by a BSPED Research award and an Academy of Medical Sciences Starter Grant for Clinical Lecturers.