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Are estrogens carcinogenic during development of the testes?
J A McLachlan1, R R Newbold, S Li
1Tulane/Xavier Center for Bioenvironmental Research, Tulane University, New Orleans, LA 70112-2699, USA.
Summary
Environmental estrogens like diethylstilboestrol (DES) can impact male reproductive development. Prenatal exposure to DES in mice led to testicular diseases and altered gene regulation, suggesting developmental risks.
Area of Science:
- Reproductive Toxicology
- Developmental Biology
- Endocrinology
Background:
- Environmental chemicals can mimic estrogen, posing risks to reproductive health.
- Prenatal exposure to estrogens is a suspected factor in testicular diseases.
Purpose of the Study:
- To investigate the mechanisms of estrogenic chemical action during male genital tract differentiation.
- To study the effects of developmental exposure to diethylstilboestrol (DES) on reproductive development.
Main Methods:
- Developmental exposure of mice to the synthetic estrogen diethylstilboestrol (DES).
- Assessment of reproductive health outcomes, including semen quality, prostatic disease, and testicular neoplasia.
- Analysis of estrogen-responsive gene regulation (lactotransferrin) and DNA methylation patterns.
Main Results:
- Prenatal DES exposure in mice caused poor semen quality, prostatic disease, cryptorchidism, and testicular neoplasia.
- A rare testicular cancer (rete testis carcinoma) was observed in 5% of in utero DES-exposed male mice.
- Altered lactotransferrin gene regulation and methylation were observed in reproductive tracts of exposed mice, indicating permanent changes.
Conclusions:
- Developmental exposure to estrogenic compounds can induce permanent alterations in the reproductive tract.
- Undifferentiated cells may be susceptible to estrogenic disruption, leading to neoplasia and developmental defects.
- Altered gene methylation serves as a potential marker for hormonal effects during critical developmental periods.