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- Title
Low Phytoestrogen Levels in Feed Increase Fetal Serum Estradiol Resulting in the "Fetal Estrogenization Syndrome" and Obesity in CD-1 Mice.
- Authors
Ruhlen, Rachel L.; Howdeshell, Kembra L.; Mao, Jiude; Taylor, Julia A.; Bronson, Franklin H.; Newbold, Retha R.; Welshons, Wade V.; vom Saal, Frederick S.
- Abstract
BACKGROUND: Although estrogenic chemicals can disrupt development of the reproductive system, there is debate about whether phytoestrogens in soy are beneficial, benign, or harmful. OBJECTIVES: 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. METHODS: The low-phytoestrogen diet was non-soy PMI 5K96 (verified casein diet), and the highphytoestrogen diet consisted of soy-based PMI 5008 during pregnancy and lactation and soy-based PMI 5001 maintenance feed after weaning. RESULTS: 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. CONCLUSIONS: 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.
- Subjects
PHYTOESTROGENS; SOYFOODS; MICE; ANIMAL feeds; OBESITY; REPRODUCTIVE health; PRECOCIOUS puberty; PHYSIOLOGICAL effects of glucose; ESTRADIOL; PHYSIOLOGICAL adaptation
- Publication
Environmental Health Perspectives, 2008, Vol 116, Issue 3, p322
- ISSN
0091-6765
- Publication type
Article
- DOI
10.1289/ehp.10448