Reproductive tract calculi, their induction, age incidence, composition and biological effects in Balb/c Crgl mice injected as newborns with estradiol-17 beta.

Abstract

Preputial and vaginal stone formation and a variety of other severe effects on the reproductive tract were observed in 5- and 1 0-month-old Balb/c mice after injection of 50 �g estradiol-1 713/day for the first 5 days of life. Weight and frequency of stones in females increased with age and urine pH. Urine pH and weight of stones increased but frequency of stones decreased with age in males. Vaginal calculi contained more calcium, but their elemental composition was otherwise similar to preputial stones. Crystalline structure varied with age and sex and the shift from apatite to struvite coincided with the presence of inflammation in both sexes. A syndrome of infertility, severe genital infection, testicular atrophy and necrosis, seminal vesicle and prostatic atrophy, formation of epididymal cysts and senile epithelial hyperplasia and dysplasia was also present in males. Stone deposition was not dependent on the presence of urine stasis. Female mice injected with testosterone as newborns developed small concretions in the vaginal fornix in 37% of animals by 10 months of age. Similar urinary and reproductive tract abnormalities are induced by perinatal estrogen in female humans and rodents. Our studies show that there are also major reproductive and urinary effects of perinatal estradiol in male rodents. Male humans should be closely monitored for similar sequelae after early life exposure to estradiol.