Selecting the Appropriate Rodent Diet for Endocrine Disruptor Research and Testing Studies

Abstract

Selecting the optimum diet for endocrine disruptor (ED) research and testing studies in rodents is critical because the diet may determine the sensitivity to detect or properly evaluate an ED compound. Dietary estrogens can profoundly influence many molecular and cellular event actions on estrogen receptors and estrogen-sensitive genes. The source, concentration, relative potency, and significance of dietary estrogens in rodent diets are reviewed, including dietary factors that focus specifically on total metabolizable energy and phytoestrogen content, which potentially affect ED studies in rodents. Research efforts to determine dietary factors in commercially available rodent diets that affect uterotrophic assays and the time of vaginal opening in immature CD-1 mice are summarized. A checklist is provided of important factors to consider when selecting diets for ED research and testing studies in rodents. Specific metabolizable energy levels are recommended for particular bioassays. Discussions include the between-batch variation in content of the phytoestrogens daidzein and genistein, the effects of total metabolizable energy and phytoestrogens on the timing (i.e., acceleration) of vaginal opening, and increased uterine weight in immature CD-1 mice. It is concluded that rodent diets differ significantly in estrogenic activity primarily due to the large variations in phytoestrogen content; therefore animal diets used in all ED studies should ideally be free of endocrine-modulating compounds.

Xenopus laevis is a potential alternative model animal species to study reproductive toxicity of phytoestrogens

“…Simultaneously, some authors reported that there are no significant effects of phytoestrogens in rodents (Roberts et al, 2000;Mitchell et al, 2001;Lamartiniere et al, 2002). One of the explanations for these inconsistent results is that commercial rodent diets all contain high and variable levels of abundant phytoestrogens, which could affect results of studies on reproductive toxicity of test phytoestrogens (Odum et al, 2001;Stroheker et al, 2003;Naciff et al, 2004;Thigpen et al, 2004). In this study, X. laevis tadpoles were fed Daphnia and Artemia, and frogs were fed pork liver.…”

“…However, many studies involving endocrine disruptors (including phytoestrogens) with rats lack reproducibility and also show inter-laboratory inconsistencies. In addition to the complexity of the endocrine system, some researchers think that different sensitivities of model animals and variable levels of phytoestrogen in diets should be responsible for the variable results (Everitt and Foster, 2004;Naciff et al, 2004;Thigpen et al, 2004). Stokes suggests that it is critical to select appropriate animal models and diets for endocrine disruptor studies (Stokes, 2004).…”

Gender difference of androgen actions on skeletal muscle transcriptome

“…The soy-based diet used in the present and our previous (Yoshioka et al 2006) studies contains !350 mg/g of phytoestrogens (Owens et al 2003), which is a sufficient level to induce estrogenic effects in endocrine disruptor studies (Thigpen et al 2004). However, the Organization for Economic Cooperative Development study (Owens et al 2003) has concluded that the levels of phytoestrogens are acceptable for evaluation of molecular and cellular hormonal endpoints.…”

Tools to evaluate estrogenic potency of dietary phytoestrogens:A consensus paper from the EU Thematic Network “Phytohealth” (QLKI-2002-2453)

“…Therefore, it is recommended to avoid laboratory chows based on crude plant components in studies designed to test the estrogenic potency of dietary compounds. The phytoestrogenic compounds present in chow diets may significantly affect experimental outcome (Thigpen et al, 1987;Thigpen et al, 2004). Instead, purified semi-synthetic or synthetic phytoestrogen free diets are recommended.…”