Choice of animal feed can alter fetal steroid levels and mask developmental effects of endocrine disrupting chemicals

Exposure of fetuses to endocrine disrupting chemicals (EDCs), such as the estrogenic drug diethylstilbestrol (DES), disrupts development of the reproductive system and affects other aspects of adult phenotype including diseases, consistent with the developmental origins of health and disease hypothesis. To determine whether diet could influence the effects of DES, we compared mice fed a commonly used combination of soy-based Purina 5008 (breeding and lactation) and 5001 (post-weaning) with mice fed soy-based Purina 5002 throughout life. We exposed fetal CD-1 mice (F-1) in utero on different feeds to a 0 (controls), low (0.1 mu g/kg/day) or high (50 mu g/kg/day) dose of DES via feeding the dam (F-0) on gestation days 11-17. Compared to 5008, 5002 feed significantly increased serum estradiol in control fetuses. On 5008 (but not 5002) feed, DES significantly increased fetal serum estradiol at a low dose and reduced it at a high dose. Diet influenced the effects of in utero DES on F-1 female onset of puberty and the uterine response to estradiol (an inverted-U dose-response relationship seen for DES on uterine weight with 5008/5001 feed was not observed with 5002). Both low-and high-dose DES reduced daily sperm production (DSP) in adult F-1 males on 5008/5001 feed, whereas males fed 5002 showed no DES-induced reduction in DSP. Thus, we observed a number of low-dose effects of in utero DES exposure on Purina 5008/5001 feed that were not observed using Purina 5002, a feed commonly used in industry-funded toxicological studies conducted for regulatory purposes.