Low Phytoestrogen Levels in Feed Increase Fetal Serum Estradiol Resulting in the “Fetal Estrogenization Syndrome” and Obesity in CD-1 Mice

Division of Biological Sciences, University of Missouri-Columbia, Columbia, Missouri 65211, USA.
Environmental Health Perspectives (Impact Factor: 7.98). 04/2008; 116(3):322-8. DOI: 10.1289/ehp.10448
Source: PubMed


Although estrogenic chemicals can disrupt development of the reproductive system, there is debate about whether phytoestrogens in soy are beneficial, benign, or harmful.
We compared reproductive and metabolic characteristics in male and female mice reared and maintained on non-soy low-phytoestrogen feed or soy-based high-phytoestrogen feed.
The low-phytoestrogen diet was non-soy PMI 5K96 (verified casein diet), and the high-phytoestrogen diet consisted of soy-based PMI 5008 during pregnancy and lactation and soy-based PMI 5001 maintenance feed after weaning.
In fetuses whose mothers consumed the low-phytoestrogen PMI 5K96 feed, we found a paradoxical significant elevation in endogenous serum estradiol, which was associated postnatally with adverse reproductive outcomes referred to as the "fetal estrogenization syndrome (FES)". In females, this syndrome included early puberty and increased uterine responsiveness to estrogen, and in males, it included reduced testis, epididymis, and seminal vesicle size, but an enlarged prostate. The low-phytoestrogen-fed males and females were lighter at birth, but, between weaning and adulthood, they became obese and developed abnormally high serum leptin levels; these males, but not females, showed impaired glucose regulation.
Removing phytoestrogens from mouse feed produces an obese phenotype consistent with metabolic syndrome, and the associated reproductive system abnormalities are consistent with FES due to elevated endogenous fetal estradiol. Laboratory rodents may have become adapted to high-phytoestrogen intake over many generations of being fed soy-based commercial feed; removing all phytoestrogens from feed leads to alterations that could disrupt many types of biomedical research.

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    • "First, endocrine disruptors are ubiquitous in the environment (Baillie-Hamilton, 2002; Colborn et al., 1993; Simonich and Hites, 1995). Second, they affect energy balancing systems (Heindel, 2003; Mackay et al., 2013; Manikkam et al., 2013; Newbold et al., 2005; Oken and Gillman, 2003; Ruhlen et al., 2008; Skinner et al., 2013; Tracey et al., 2013; Vom Saal et al., 2012). Third, energy balancing phenotypes are sexually dimorphic in humans, with the masculine phenotype most closely linked to metabolic diseases such as type II diabetes and heart disease (Bonora, 2000; Kotani et al., 1994; Lemieux, 2001; Macotela et al., 2009; Wajchenberg, 2000). "
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