Mammary gland differentiation by early life exposure to enantiomers of the soy isoflavone metabolite equol

Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center and the Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association (Impact Factor: 2.9). 11/2010; 48(11):3042-50. DOI: 10.1016/j.fct.2010.07.042
Source: PubMed


The role of soy in reducing breast cancer risk has been suggested to be associated with early exposure to isoflavones, which alter mammary gland morphology. The objective of the study was to determine the effect of dietary exposure to the enantiomers of a key soy isoflavone metabolite, equol, on mammary gland development and later chemoprotection using the DMBA-induced animal model of breast cancer. Animals were exposed to S-(-)equol or R-(+)equol (250 mg/kg diet) during the neonatal (0-21 days) or prepubertal (21-35 days) periods only. Histological evaluation of the mammary glands showed that both enantiomers fed neonatally via the dam led to significant precocial mammary gland differentiation. By day 50, early S-(-)equol or R-(+)equol exposure resulted in a decrease in immature terminal end structures and an increase in mature lobules, suggesting an early 'imprinting' effect. Despite these morphological changes to the mammary gland, neonatal and prepubertal exposure to equol had no long-term chemoprevention against mammary tumors induced by DMBA, although for R-(+)equol there was a trend to delaying tumor formation. In summary, early exposure to equol was not chemopreventive, but neither did it increase tumor formation in response to DMBA, suggesting exposure in early life does not influence breast cancer risk.

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    • "Several animal studies have shown that genistein given subcutaneously before puberty reduced the number and delayed the appearance of mammary tumors induced by DMBA (6, 17, 25, 40). Moreover, in contrast to adult exposure, prepubertal exposure to purified genistein and neonatal exposure to equol has also been associated with a reduction in the number of terminal end buds (TEBs, a marker of increased mammary gland differentiation ) (5,6,16,32,37). Therefore, consumption of isoflavones during early development when endogenous estrogens are low may actually increase differentiation in mammary tissues, which in turn may be responsible for the decrease in breast cancer risk associated with early soy consumption (47). Some animal studies have tested SPI rather than genistein. "
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