Pups of beagles were injected with 200 ng estradiol benzoate/kg body weight 5 times weekly during the first 6 weeks of life. The hip joints of the pups were particularly studied. At 6 weeks of age hip joint laxity was present in all the injected pups and the femoral heads were smaller than those of the controls. Radiographic studies showed earlier development of ossification centers in the femoral heads. The over-all weight gain of the treated pups was normal. Pregnant beagle bitches were injected with estradiol benzoate during the last 3 weeks of gestation. Intramuscular injection of more than 90 μg estradiol benzoate/kg body weight resulted in intrauterine fetal death. Lower doses caused developmental changes, but did not affect the fetal mortality. Changes in the hip joints were observed in the offspring at 6 weeks of age; joint laxity was present and the femoral heads were smaller than those of controls. The weight gain was lower than normal. The results indicate that administration ofestradiol to bitches during pregnancy causes changes in their pups similar to those observed when estradiol is injected directly to pups during the first 6 weeks of life. (Endocrinology85: 481, 1969)
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Gustafsson et al. (1969) studied this question.