Are estrogens carcinogenic during development of the testes?
Many chemicals in the environment mimic the female sex hormone, estrogen. Exposure to environmental estrogens during early fetal development was proposed by Sharpe & Skakkebaek as a potential risk factor for subsequent testicular disease, including neoplasia and poor semen quality. To understand the mechanisms of action of estrogenic chemicals during differentiation of the male genital tract, we have studied developmental exposure to the synthetic estrogen, diethylstilboestrol (DES). While DES is a much more potent estrogen than most environmental chemicals examined, several of these compounds share some of the same properties as DES, such as a relative lack of binding to serum estrogen carrying proteins. Prenatal exposure to DES is associated with poor semen quality, prostatic disease, cryptorchidism and testicular neoplasia in mice. A rare form of testicular cancer, rete testis carcinoma, was observed in five percent of male mice treated in utero with DES. We also demonstrated altered regulation of an estrogen responsive gene, lactotransferrin (LTF) in the seminal vesicles of treated mice, but not the controls. Likewise, LTF was irreversibly altered in the uteri of developmentally treated females; at the molecular level altered methylation of the gene appears to be involved, thus, providing a potential marker for hormonal effects during development. The induction of permanent or "imprinted" responses during the development of a relatively estrogen-free reproductive tract cell suggests that undifferentiated targets for estrogen action may be sites for subsequent growth and differentiation defects associated with neoplasia.
McLachlan
J A
JA
Tulane/Xavier Center for Bioenvironmental Research, Tulane University, New Orleans, LA 70112-2699, USA.
Newbold
R R
RR
Li
S
S
Negishi
M
M
D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D004054:Diethylstilbestrol / Q000633:toxicity; D004967:Estrogens / Q000009:adverse effects / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D012307:Risk Factors; D013736:Testicular Neoplasms / Q000209:etiology / Q000473:pathology*; D013737:Testis / Q000196:embryology / Q000473:pathology* / Q000502:physiology*
D002273:Carcinogens; D004967:Estrogens; D004054:Diethylstilbestrol