BACKGROUND: Permanent abnormalities have been reported in reproductive and non-reproductive organs of mice and humans exposed perinatally to a synthetic estrogen, diethylstilbestrol (DES). Recent studies demonstrated that sex hormones affected the shape of the innominate bone in mice. Therefore, we analyzed the long-term effects of neonatal exposure of DES and tamoxifen, an anti-estrogen, in mouse bones. METHODS: Changes in the pelvis and femur were examined in 1- to 15-month-old C57BL/Tw male mice given 5 daily injections of 3 micrograms DES or of 100 micrograms tamoxifen beginning on the day of birth by measuring contents of calcium (Ca) and phosphorus (P), and the numbers of osteoblasts and osteoclasts. RESULTS: The ash weight of pelvis and femur in neonatally DES- and tamoxifen-treated mice was lower than that in the controls at 2-15 months of age. Contents of Ca and P of pelvis and femur in neonatally tamoxifen-treated mice were lower than in the controls and neonatally DES-treated mice. In neonatally DES-treated mice at 6-12 months, Ca and P contents in the pelvis were lower than in controls, but not different in the femur. The number of osteoblasts per unit length of endocortical surface of the femur in 2- and 3-month-old DES- and tamoxifen-treated mice was lower than that in the controls. The osteoclast number in the femur in DES-treated mice at 2 to 12 months was not different from that in the controls; however, in tamoxifen-treated mice, the number was higher than in the controls. An epiphyseal line was clearly detected in the femur of 12- and 15-month-old DES- and tamoxifen-treated male mice, whereas the line in the controls disappeared after 12 months. CONCLUSIONS: The present results indicate that in male mice, neonatal exposure to DES and tamoxifen induced permanent changes in the pelvis and the femur, and that tamoxifen had a greater effect on bone tissue than did DES.
BACKGROUND: Permanent abnormalities have been reported in reproductive and non-reproductive organs of mice and humans exposed perinatally to a synthetic estrogen, diethylstilbestrol (DES). Recent studies demonstrated that sex hormones affected the shape of the innominate bone in mice. Therefore, we analyzed the long-term effects of neonatal exposure of DES and tamoxifen, an anti-estrogen, in mouse bones. METHODS: Changes in the pelvis and femur were examined in 1- to 15-month-old C57BL/Tw male mice given 5 daily injections of 3 micrograms DES or of 100 micrograms tamoxifen beginning on the day of birth by measuring contents of calcium (Ca) and phosphorus (P), and the numbers of osteoblasts and osteoclasts. RESULTS: The ash weight of pelvis and femur in neonatally DES- and tamoxifen-treated mice was lower than that in the controls at 2-15 months of age. Contents of Ca and P of pelvis and femur in neonatally tamoxifen-treated mice were lower than in the controls and neonatally DES-treated mice. In neonatally DES-treated mice at 6-12 months, Ca and P contents in the pelvis were lower than in controls, but not different in the femur. The number of osteoblasts per unit length of endocortical surface of the femur in 2- and 3-month-old DES- and tamoxifen-treated mice was lower than that in the controls. The osteoclast number in the femur in DES-treated mice at 2 to 12 months was not different from that in the controls; however, in tamoxifen-treated mice, the number was higher than in the controls. An epiphyseal line was clearly detected in the femur of 12- and 15-month-old DES- and tamoxifen-treated male mice, whereas the line in the controls disappeared after 12 months. CONCLUSIONS: The present results indicate that in male mice, neonatal exposure to DES and tamoxifen induced permanent changes in the pelvis and the femur, and that tamoxifen had a greater effect on bone tissue than did DES.