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Effects of in utero exposure to nonsteroidal estrogens on mouse testis
C Pérez-Martínez1, M C Ferreras-Estrada, M J García-Iglesias
1Department of Animal Pathology, Animal Medicine, Faculty of Veterinary Science, University of León, Spain.
Abstract:
Male mice exposed in utero to alpha-zearalanol (zeranol) or diethylstilbestrol (DES) were analyzed postnatally to evaluate the possible changes on their testicular morphology as part of an examination of the effects of transplacental exposure to non-steroidal estrogens on sensitive tissues. Pregnant NMRI mice were injected subcutaneously with ethyl oleate (0.1 mL) alone (negative control) or with 150 micrograms/kg of body weight of zeranol or DES (positive control) on days 9 and 10 of gestation. Experimental and control male offspring were euthanized at days 45 (n = 47), 90 (n = 44), 180 (n = 40) and 365 (n = 26) after birth and their gonads were examined by light and electron microscopy. The results suggested that prenatal zeranol or DES exposure induced more severe and earlier (at 45 d) testicular abnormalities than in negative control (at 6 mo). These age-related alterations were characterized by regressive changes in the germinal epithelium and Sertoli's cells as well as foci of Leydig's cells around atrophied seminiferous tubules and dysplasia of the rete testis epithelium. On the contrary, the presence of Leydig's cells with immature morphology and their arrangement in sheet could be attributable exclusively to estrogen treatment. The presence of no neoplasm was confirmed.
Insights
Prenatal exposure to alpha-zearalanol (zeranol) or diethylstilbestrol (DES) caused early and severe testicular abnormalities in male mice. These estrogenic effects included regressive changes in germinal and Sertoli cells, and Leydig cell abnormalities.
Area of Science:
- Endocrinology
- Reproductive Biology
- Toxicology
Background:
- Transplacental exposure to endocrine-disrupting chemicals can impact sensitive tissues.
- Non-steroidal estrogens, like zeranol and diethylstilbestrol (DES), are known to affect reproductive development.
Purpose of the Study:
- To evaluate the effects of in utero exposure to zeranol and DES on male mouse testicular morphology.
- To examine age-related changes in testicular tissues following prenatal estrogenic exposure.
Main Methods:
- NMRI mice were exposed to zeranol or DES during gestation (days 9-10).
- Male offspring were analyzed at postnatal days 45, 90, 180, and 365.
- Testicular tissues were examined using light and electron microscopy.
Main Results:
- Prenatal zeranol or DES exposure led to earlier and more severe testicular abnormalities compared to controls.
- Observed alterations included germinal epithelium and Sertoli cell regression, Leydig cell foci, and rete testis dysplasia.
- Immature Leydig cells and their sheet-like arrangement were specific to estrogen-treated groups; no neoplasms were found.
Conclusions:
- In utero exposure to zeranol and DES induces significant, dose-dependent testicular abnormalities in male mice.
- These findings highlight the sensitivity of developing reproductive tissues to estrogenic compounds.
- The study confirms the potential for transplacental exposure to cause lasting reproductive tract damage.