The 25th Volume: President's Message: Andrology in the 20th Century: A Commentary on Our Progress During the Past 25 Years

Prins, Gail S.; Bremner, William J.

doi:10.1002/j.1939-4640.2004.tb02812.x

Cited by 7 publications

(1 citation statement)

References 30 publications

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“…Prins and colleagues reported that neonatal estrogen (E2) exposure induced lobe-specific alterations in the adult rat prostate, including a permanent decrease in androgen receptor (AR) levels (Prins 1992; Prins et al 1993). In a study using the neonatal DES model, Prins and Bremner (2004) reported an abnormal morphology of the penis in male rats associated with changes in the protein levels of ERα, but not AR. In addition, neonatal DES exposure has been reported to significantly decrease the level of ERα protein in the anterior prostate but increase its level in the SV of male mice (Turner et al 1989).…”

Section: Introductionmentioning

confidence: 99%

Diethylstilbestrol (DES)-Stimulated Hormonal Toxicity is Mediated by ER α Alteration of Target Gene Methylation Patterns and Epigenetic Modifiers ( DNMT3A , MBD2 , and HDAC2 ) in the Mouse Seminal Vesicle

Li¹,

Hamilton²,

Lai

et al. 2014

Environ Health Perspect

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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.Citation: Li Y, Hamilton KJ, Lai AY, Burns KA, Li L, Wade PA, Korach KS. 2014. Diethylstilbestrol (DES)-stimulated hormonal toxicity is mediated by ERα alteration of target gene methylation patterns and epigenetic modifiers (DNMT3A, MBD2, and HDAC2) in the mouse seminal vesicle. Environ Health Perspect 122:262–268; http://dx.doi.org/10.1289/ehp.1307351

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