Neonatal exposure to diethylstilbestrol alters expression of DNA methyltransferases and methylation of genomic DNA in the mouse uterus

Koji Sato, Hideki Fukata, Yasushi Kogo, Jun Ohgane, Kunio Shiota, Chisato Mori

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Perinatal exposure to diethylstilbestrol (DES) can have numerous adverse effects on the reproductive organs later in life, such as vaginal clear-cell adenocarcinoma. Epigenetic processes including DNA methylation may be involved in the mechanisms. We subcutaneously injected DES to neonatal C57BL/6 mice. At days 5, 14, and 30, expressions of DNA methyltransferases (Dnmts) Dnmtl, Dnmt3a, and Dnmt3b, and transcription factors Spl and Sp3 were examined. We also performed restriction landmark genomic scanning (RLGS) to detect aberrant DNA methylation. Real-time RT- PCR revealed that expressions of Dnmtl, Dnmt3b, and Sp3 were decreased at day 5 in DES-treated mice, and that those of Dnmtl, Dnmt3a, and Spl were also decreased at day 14. RLGS analysis revealed that 5 genomic loci were demethylated, and 5 other loci were methylated by DES treatment. Two loci were cloned, and differential DNA methylation was quantified. Our results indicated that DES altered the expression levels of Dnmts and DNA methylation.

Original languageEnglish
Pages (from-to)131-139
Number of pages9
JournalEndocrine Journal
Volume56
Issue number1
DOIs
Publication statusPublished - 2009
Externally publishedYes

    Fingerprint

Keywords

  • Diethylstilbestrol
  • DNA methylation
  • Endocrine disruptor
  • Epigenetics
  • Uterus

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this