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SECOND INTERNATIONAL SYMPOSIUM
ON THE ROLE OF SOY
IN PREVENTING AND TREATING CHRONIC DISEASESeptember 15-18, 1996
Brussells, Belgium
POSTER ABSTRACTSPermanent Effects of Neonatal Coumestrol and Equol Treatment in Rats
Daniel M. Sheehan, Kevin L. Medlock and Cynthia D. Burroughs
Division of Reproductive and Developmental Toxicology
National Center for Toxicological Research
Food and Drug Administration
Jefferson, AR 72079-9502
We have previously shown dose responsive short term adverse effects of coumestrol and equol in newborn rats (PSEBM, 208: 307-313,1995). To determine the permanence of these effects, newborn rats were injected with dimethyl sulfoxide (DMSO vehicule control) diethylstilbestrol (DES 10mg; positive control), coumestrol (COUM 100mg) or equol (E, 100mg) once daily for the first five days of life. Animals were sacrified at 6 and 10 months of age. In the uterus and increased incidence of luminal squamous metaplasia (DES-COUM>E) was seen at both 6 and 10 months. Glandular sqaumous was not significantly increased over vehicule controls at 6 months, but was marginally increased in the COUM and E groups at 10 months. At 6 and 10 months luminal and glandular epithelium heights were increased, while uterine gland numbers were decreased; the extent of change was about the same for the three estrogens. Likewise uterine estrogen receptor levels were decreased in all treatment groups at both ages. In the ovary, the number of primary and primordial follicles was decreased, the number of large and graafian follicles was increased, while cystics follicles, polyovular follicles and ceroid depostion were increased in all treatment groups. These data, taken together, demonstrate typical estrogenic toxicological affects, with DES and COUM showing greater effects than E for some measures at the doses used. Additionally, these days demonstrate the power of our earlier short-term data sets to predict appropriate doses as well as the direction and magnitude of the effects.
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