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Persistent trefoil factor 1 expression imprinted on mouse vaginal epithelium by neonatal estrogenization
Fujiko Masui1, Keiko Kurosaki, Takao Mori
1Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo, 113-0033, Japan.
Cell and Tissue Research
|September 1, 2005
Summary
Neonatal estrogen exposure permanently increases trefoil factor 1 (TFF1) gene expression in the mouse vagina. This TFF1 overexpression may cause mucin accumulation and serve as a marker for developmental estrogenization syndrome.
Area of Science:
- Reproductive biology
- Developmental toxicology
- Molecular endocrinology
Background:
- Neonatal exposure to estrogenic substances can cause lasting reproductive tract defects in female mice.
- These defects include persistent epithelial proliferation and increased cancer risk in adulthood.
Purpose of the Study:
- To identify estrogen-regulated genes in the neonatal mouse vagina.
- To investigate the role of trefoil factor 1 (TFF1) in developmental estrogenization.
Main Methods:
- DNA microarray hybridization analysis to identify differentially expressed genes.
- Quantitative analysis of TFF1 mRNA expression via RT-PCR.
- Immunohistochemistry to confirm TFF1 protein localization.
Main Results:
- TFF1 mRNA expression was significantly upregulated by estrogen in neonatal mouse vagina, but not in adults.
- Neonatal estrogenization led to persistent TFF1 overexpression in adulthood.
- TFF1 protein was localized in the vaginal epithelium of neonatally estrogenized mice.
- Mucinous gel filled the vaginal lumen without changes in mucin gene expression, potentially due to TFF1 overexpression.
Conclusions:
- Estrogen directly induces permanent TFF1 gene expression in the developing mouse vagina.
- TFF1 induction is not linked to promoter hypermethylation.
- TFF1 may serve as a valuable biomarker for developmental estrogenization syndrome in mice.