In vivo induction of increased DNA ploidy of mouse cervicovaginal epithelium by neonatal estrogen treatment

The purpose of this study was to test the hypothesis that exposure to natural estrogen early in the development of hormone-dependent tissue induces a change in nuclear DNA content. Female BALB/c mice were treated neonatally with daily s.c. injections of either 25 μg of 17β-estradiol (E₂) in 0.02 ml of sesame oil (vehicle) or vehicle alone for 5 days. Treatment was begun either within 15 h of birth or 6 days after birth. One set each of 10-day- old E₂-treated and control mice received s.c. pellet implants containing 15 mg of E₂ and cholesterol (10% E₂ and 90% cholesterol), a second set received implants containing 25 mg of cholesterol alone, and a third set did not receive implants. Cervicovaginal tracts from intact BALB/c mice were examined histologically and by flow cytometry at 21, 40, 70, 180, or 240 days of age. The results obtained include several important findings: 1) neonatal E₂ treatment in BALB/c mice causes an increase in nuclear DNA content in cervicovaginal epithelium; 2) short-term administration of secondary exogenous E₂ reduces the latency period for the appearance of increased nuclear DNA content in neonatally E₂-treated cervicovaginal epithelium; 3) increased nuclear DNA content can indicate abnormal cervicovaginal epithelium before histological abnormalities become evident; and 4) there is a sensitive period for neonatal E₂ induction of increased nuclear DNA content in the cervicovaginal epithelium. These findings support other reports of the carcinogenic potential of estrogen in vivo. Therefore, increased DNA ploidy may be an important early detectable event in estrogen-induced carcinogenesis.