Diethylstilbestrol in the mouse seminal vesicle

BACKGROUND: Diethylstilbestrol (DES) is a synthetic estrogen associated with adverse effects on reproductive organs. DES-induced toxicity of the mouse seminal vesicle (SV) is mediated by estrogen receptor α (ERα), which alters expression of seminal vesicle secretory protein IV (Svs4) and lactoferrin...

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Bibliographic Details
Published in:Environmental health perspectives 2014-03, Vol.122 (3), p.262
Main Authors: Li, Yin, Hamilton, Katherine J, Lai, Anne Y, Burns, Katherine A, Li, Leping, Wade, Paul A, Korach, Kenneth S
Format: Article
Language:English
Subjects:
Diethylstilbestrol
Endocrine disruptors
Environmental aspects
Genetic aspects
Genetic research
Health aspects
Physiological aspects
Seminal vesicles
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Summary:BACKGROUND: Diethylstilbestrol (DES) is a synthetic estrogen associated with adverse effects on reproductive organs. DES-induced toxicity of the mouse seminal vesicle (SV) is mediated by estrogen receptor α (ERα), which alters expression of seminal vesicle secretory protein IV (Svs4) and lactoferrin (Ltf) genes. OBJECTIVES: We examined a role for nuclear receptor activity in association with DNA methylation and altered gene expression. METHODS: We used the neonatal DES exposure mouse model to examine DNA methylation patterns via bisulfite conversion sequencing in SVs of wild-type (WT) and ERα-knockout (αERKO) mice. RESULTS: The DNA methylation status at four specific CpGs (-160, -237, -306, and -367) in the Svs4 gene promoter changed during mouse development from methylated to unmethylated, and DES prevented this change at 10 weeks of age in WT SV. At two specific CpGs (-449 and -459) of the Ltf gene promoter, DES altered the methylation status from methylated to unmethylated. Alterations in DNA methylation of Svs4 and Ltf were not observed in αERKO SVs, suggesting that changes of methylation status at these CpGs are ERα dependent. The methylation status was associated with the level of gene expression. In addition, gene expression of three epigenetic modifiers--DNMT3A, MBD2, and HDAC2--increased in the SV of DES-exposed WT mice. CONCLUSION: DES-induced hormonal toxicity resulted from altered gene expression of Svs4 and Ltf associated with changes in DNA methylation that were mediated by ERα. Alterations in gene expression of DNMT3A, MBD2, and HDAC2 in DES-exposed male mice may be involved in mediating the changes in methylation status in the SV. 10.1289/ehp.1307351
ISSN:0091-6765
1552-9924
DOI:10.1289/ehp.1307351