Effect of rodent diets on the sexual development of the rat

Five rodent diets have been evaluated for their possible effect on the sexu al development of the rat. Groups of 12 pregnant Alpk rats were fed one of the following combinations of diets during; pregnancy and postnatally: RM3/ RM1, AIN-76A/AIN-76A, RM3/ AIN-76A, Teklad Global 2016 (Global)/Global and Purina 5001/ Purina 5001. AIN-76A is phytoestrogen-free while the other die ts contained varying amounts of phytoestrogens. The phytoestrogens genistei n and daidzein were determined in the diets studied, and the concentrations found agreed with earlier estimates, RM3/RM1 was selected as the control g roup, as this has been used routinely in this laboratory for the past decad e, Determinations were made in offspring of the times of vaginal opening an d first estrus among the females, and of prepuce separation and testes desc ent among the males, At postnatal day (PND) 26 the females from 6 of the 12 litters were terminated and tissue weights measured. Males from 6 of the 1 2 litters were similarly studied at PND 68, Animals from the remaining litt ers were transferred to RM1 diet at PND 70, Termination of the study was at PND 128 (males) and PND 140 (females) when body weights and tissue weights were determined. Marked differences in body weight, sexual development, and reproductive tis sue weights were observed for rats maintained on AIN-76A or Purina 5001, wi th only minimal effects among rats maintained on the Global diet. These com parisons were against RM3/RM1 as the reference diet. However, using Purina 5001 as the reference diet reversed the direction of the differences seen w hen using RM3/RM1 as the reference diet, The differences observed when usin g RM3/RM1 as reference diet occurred mainly postnatally. In addition, the f act that similar differences were seen for the phytoestrogen-free diet, AIN -76A, and the phytoestrogen-rich diet, Purina 5001, indicate that these eff ects are more likely to be caused by nutritional differences between the di ets that then have centrally mediated effects on rodent sexual development, rather than individual dietary components affecting peripheral estrogen re ceptors (ER), This proposal is supported by abolition of the uterotrophic a ctivity of AIN-76A and Purina 5001 (relative to RM3/RM1) in the immature ra t by coadministration of the gonadotrophin-releasing hormone (GnRH) antagon ist Antarelix. The present data indicate that choice of diet may influence the timing of s exual development in the rat, and consequently, that when evaluating the po tential endocrine toxicity of chemicals, the components of rodent diets use d should be known, and as far as is possible, controlled.