Abstract
Neonatal administration of estradiol-17β (E2-17β) increases the nuclear DNA content in the mouse reproductive tract. Similar responses have been demonstrated for synthetic estrogens such as diethylstilbestrol. One of the questions raised regarding environmental estrogens such as organochlorines is whether they are potent enough to result in abnormal changes such as those demonstrated by both natural and synthetic estrogens. To test this hypothesis, female BALB/c mice were treated neonatally (days 1-5) with either E2-17β or estradiol-17α (E2-17α), an inactive stereoisomer in adult reproductive tissues. We also proposed whether neonatal administration of (E2-17α) was tumorigenic and whether the effects were age dependent. To answer these questions, one set each of 10-day-old treated and control mice received short-term secondary administration of E2-17β, E2-17α, or cholesterol. Cervicovaginal tracts from intact BALB/c mice were examined histologically and by flow cytometry at 70 days of age and by histology alone at 18 to 22 months of age. The results include several important findings: a) like E2-17β, neonatal E2-17α treatment induced persistent vaginal cornifcation, hypospadias, vaginal concretions, and hyperproliferation in nearly 100% of the animals regardless of the secondary treatment for most groups; b) neonatal E2-17α treatment increased the nuclear DNA content of cervicovaginal epithelium at one-half both the level (mean DNA index of 1.02 vs 1.04) and incidence (22 vs 46% of the animals) of E2-17β; c) short-term secondary treatment with E2-17α, unlike E2-17β, did not significantly augment the increase in DNA content (13% for E2-17α vs 37 and 56% for control and E2-17β, respectively); and d) neonatal administration with E2-17α induced adenosquamous tumors in the reproductive tract in 25% of the animals. Therefore, the biological effects (estrogenic potency) of E2-17α may be age dependent.
Original language | English (US) |
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Pages (from-to) | 577-581 |
Number of pages | 5 |
Journal | Environmental Health Perspectives |
Volume | 105 |
Issue number | SUPPL. 3 |
DOIs | |
State | Published - Apr 1997 |
Keywords
- Carcinogen
- Cervicovaginal
- Development
- Endocrine disruptor
- Estradiol
- Estrogen
- Mouse
- Neonatal
ASJC Scopus subject areas
- Public Health, Environmental and Occupational Health
- Health, Toxicology and Mutagenesis