title: p21 and Notch signalings in the persistently altered vagina induced by neonatal diethylstilbestrol exposure in mice.
abstract: Female reproductive organs show organ-specific morphological changes during estrous cycles. Perinatal exposure to natural and synthetic estrogens including diethylstilbestrol (DES) or estrogenic chemicals induces estrogen-independent persistent proliferation of vaginal epithelium in mice. To understand the underlying mechanism of the estrogen-independent persistent vaginal changes induced by perinatal DES exposure, we examined global gene expressions in the vaginae of ovariectomized adult mice exposed neonatally to DES using a microarray. The cell cycle-related gene, p21, a cyclin-dependent kinase inhibitor, showed upregulation in the vagina, and p21 protein was localized in the basal layer of the vaginal epithelium in mice exposed neonatally to DES and an estrogen receptor α agonist, propyl pyrazole triol (PPT). The expressions of Notch receptors and Notch ligands were unchanged; however, the mRNAs of hairy-related basic helix-loop-helix (bHLH) transcription factor genes, Hes1, Hey1 and Heyl were persistently downregulated in the vagina, indicating estrogen-independent epithelial cell proliferation in mice exposed neonatally to DES and PPT.
authors: Department of Material and Biological Chemistry, Faculty of Science, Yamagata University, Kojirakawa-machi, Yamagata 990-8560, Japan.
authors: Takeshi
authors: T
authors: Nakamura
authors: Shinichi
authors: S
authors: Miyagawa
authors: Yoshinao
authors: Y
authors: Katsu
authors: Takeshi
authors: T
authors: Mizutani
authors: Tomomi
authors: T
authors: Sato
authors: Takashi
authors: T
authors: Takeuchi
authors: Taisen
authors: T
authors: Iguchi
authors: Yasuhiko
authors: Y
authors: Ohta
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004054:Diethylstilbestrol; D004847:Epithelial Cells / Q000187:drug effects*; D004968:Estrogens, Non-Steroidal / Q000009:adverse effects*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014621:Vagina / Q000166:cytology* / Q000187:drug effects
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004054:Diethylstilbestrol; D004968:Estrogens, Non-Steroidal; D051880:Receptors, Notch