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DO BODY WEIGHT CHANGES IMPACT AGE OF PUBERTY AND REPRODUCTIVE ENDPOINTS IN THE EDSP TIER 1 MALE AND FEMALE PUBERTAL PROTOCOLS?
Citation:
Stoker, T E., J M. Ferrell, W. K. McElroy, K Bremser, R L. Cooper, AND S C. Laws. DO BODY WEIGHT CHANGES IMPACT AGE OF PUBERTY AND REPRODUCTIVE ENDPOINTS IN THE EDSP TIER 1 MALE AND FEMALE PUBERTAL PROTOCOLS? Presented at Serono Pubertal Workshop, Chicago, IL, November 6-8, 2003.
Description:
DO BODY WEIGHT CHANGES IMPACT AGE OF PUBERTY AND REPRODUCTIVE ENDPOINTS IN THE EDSP TIER 1 MALE AND FEMALE PUBERTAL PROTOCOLS? T.E. Stoker, K. McElroy, J. Ferrell, K. Bremser, R. Cooper and S.C. Laws. Endocrinology Branch, RTD, NHEERL, ORD, USEPA, RTP, NC.
The relationship between growth and puberty has been the focus of numerous studies for several decades. In brief, those studies have shown that major fluctuations in body weight (bw) will clearly influence the age at which the male and female undergo sexual maturation. On the other hand, what has become more contentious is the impact that a small (i.e., <10%) decrease in bw may have on puberty. Indeed, one criticism of the EDSP Tier 1 pubertal protocols is that the outcome of any study employing puberty as an endpoint will be impacted by any change in bw, enhancing the probability of false positives or false negatives when chemicals are tested. The male and female pubertal protocols were designed to detect endocrine disrupting chemicals that alter the onset of puberty and thyroid function. One concern is that a nonspecific reduction in bw may confound the interpretation of any effect on the endocrine endpoints of interest. To elucidate the relationship between bw and pubertal development, male and female Wistar rats were underfed to 90, 80, 70 and 60% of controls fed ad libitum. Females were underfed from postnatal day (PND) 22-42. This regimen decreased terminal bw 1.8, 4.1, 12.1, and 18.8% of ad libitum controls. Vaginal opening, uterine weight (wt) and thyroid hormones were not altered in any of the underfed females. Although decreases in bw of 12.1 and 18.8% did significantly lower absolute ovarian wt, relative ovarian wt was not affected. Thus, there were no significant differences in any of the female reproductive endpoints measured in accordance with the female pubertal protocol. Underfeeding males from PND 23-53 resulted in terminal bw decreases of 2.0, 6.0, 9.0, and 19.5% of ad libitum controls. Preputial separation, epididymal and testes wts were the same as control males in all underfed groups. Although a significant decrease in the absolute wt of the ventral prostate and seminal vesicle was noted in males with a 19.5% decrease in bw, the relative wts of these tissues were not different than controls. A decrease in thyroid stimulating hormone was observed in males with a 19.5% reduction in bw, while both T3 and T4 were significantly reduced in males with a 9 and 19.5% reduction in bw. Importantly, there were no significant alterations of the male reproductive endpoints at less than 9.0% decreased bw. These data demonstrate that reduced bw over a range of 2-9% do not confound the reproductive endpoints in either pubertal protocol and that keeping the dose range of the tested compounds below the MTD (<10% reduction in bw) will provide valid data on the effects of the test compounds on these endocrine endpoints. (Abstract does not reflect EPA policy)