Variations in Phytoestrogen Content between Different Mill Dates of the Same Diet Produces Significant Differences in the Time of Vaginal Opening in CD-1 Mice and F344 Rats but Not in CD Sprague-Dawley Rats

Abstract

BackgroundThe optimum test diet and rodent species/strain for evaluating endocrine-disrupting compounds (EDCs) are critical.ObjectivesWe conducted studies to evaluate rodent species sensitivity and the effects of diets varying in phytoestrogen content on the time of vaginal opening (VO) in CD-1 mice, Fischer 344 (F344) rats, and CD Sprague-Dawley (S-D) rats.MethodsMice were weaned on postnatal day (PND) 15 and rats on PND19 and randomly assigned to control or test diets. Body weights, food consumption, and time of VO were recorded.ResultsThe time of VO was significantly advanced in F344 rats fed diets containing daidzein and genistein, whereas these same diets did not advance VO in S-D rats. When animals were fed the AIN-76A diet spiked with genistein, time of VO was significantly advanced at all doses in CD-1 mice, at the two highest doses in F344 rats, and at the highest dose in S-D rats. The time of VO in F344 rats was more highly correlated with the phytoestrogen content than with the total metabolizable energy (ME) of 12 diets.ConclusionsThe S-D rat is less sensitive to dietary phytoestrogens compared with the F344 rat or the CD-1 mouse, suggesting that the S-D rat is not the ideal model for evaluating estrogenic activity of EDCs. The profound effects of dietary phytoestrogens on the time of VO, an estrogen-sensitive marker, indicate that a standardized open-formula phytoestrogen-free diet containing a low ME level should be used to optimize the sensitivity of estrogenic bioassays.

The Role of Neurokinin B Signalling in Reproductive Neuroendocrinology

“…There is perhaps a physiological threshold of circulating E 2 levels, which sees reversal of the NKB-induced stimulation of LH secretion. This threshold is likely to be species- and even strain-specific, since the polymorphisms that distinguish the structures of oestrogen receptor-α expressed by different rat strains [62] are potentially capable of giving rise to differences in sensitivity to E 2 [63,64,65,66,67]. However, the mechanism whereby NKB can both stimulate and suppress LH secretion remains cryptic.…”

Comparison of endpoints relevant to toxicity assessments in 3 generations of CD-1 mice fed irradiated natural and purified ingredient diets with varying soy protein and isoflavone contents

“…In the case of studies of potential endocrine disruptors, and, in particular, agents with potential estrogenic activity, there has been much concern about the possible confounding effects of soy components, particularly estrogenic soy isoflavones (Boettger-Tong et al, 1998; Muhlhauser et al, 2009; Patisaul et al, 2012; Thigpen et al, 2004; Wang et al, 2005). This focus is due to the widespread use of varying levels of soy meal in natural ingredient diets typically used in rodent studies and fluctuations in isoflavone levels in diets of equivalent amounts of soy meal based on weather and other growing conditions (Brown and Setchell, 2001; Heindel and vom Saal, 2008; Thigpen et al, 2007; Thigpen et al, 1999). The interpretation of studies on the impact of diets containing soy is complicated by the presence of many non-isoflavone bioactive components in soy meal that can vary independently of the isoflavones (Kang et al, 2010; Velasquez and Bhathena, 2007).…”

A review of seasonal/circannual effects of laboratory rodent behavior

“…Still, researchers and animal care workers move from the outdoor environment into the vivarium and small particles may be carried inside via this route. Secondly, although nutrient content may remain constant, the composition of laboratory rodent diets may vary with season or mill date (e.g., [57][58][59]). Nevertheless, there is no evidence that these two possible sources have any direct influence on potential circannual or seasonal rhythms.…”