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Enhanced ERbeta immunoexpression and apoptosis in the germ cells of cimetidine-treated rats
1Department of Morphology, Laboratory of Histology and Embryology, Dental School of São Paulo State University, Rua Humaitá, 1680, CEP: 14801-903, Araraquara (São Paulo), Brazil. esasso@foar.unesp.br
Background:
Cimetidine, refereed as antiandrogenic drug, causes hormonal changes in male patients such as increased testosterone and FSH levels. In the rat testis, structural alterations in the seminiferous tubules have been related to germ cell loss and Sertoli cell death by apoptosis. Regarding the important role of Sertoli cells in the conversion of testosterone into estrogen, via aromatase, the immunoexpression of estrogen receptors-beta (ERbeta) was evaluated in the germ cells of untreated and treated rats with cimetidine. A relationship between ERbeta immunoreactivity and apoptosis was also investigated in the germ cells of damaged tubules.
Methods:
Immunohistochemistry for detection of ERbeta and TUNEL method were performed in testicular sections of adult male rats treated with 50 mg/Kg of cimetidine (CmG) or saline solution (CG) for 52 days.
Results:
In CG, a cytoplasmic immunoexpression for ERbeta was observed in spermatogonia, primary spermatocytes and spermatids. An evident ERbeta immunoreactivity was always observed in the flagellum and residual bodies of late spermatids. In CmG, the cytoplasm or cytoplasm and nuclei of germ cells of the damaged tubules by cimetidine showed enhanced ERbeta immunostaining. TUNEL-labeling was usually observed in the same germ cell types exhibiting enhanced ERbeta immunoreactivity.
Conclusion:
The presence of ERbeta immunolabeling in the flagellum and residual bodies of spermatids reinforces the role of estrogen in spermiogenesis. The overexpression of ERbeta in the germ cells of CmG could be related to a possible interference of cimetidine on tubular androgenization and/or on the intratubular aromatase due to Sertoli cell damage. The parallelism between ERbeta overexpression and apoptosis indicates a participation of ERbeta on germ cell death.
Insights
Cimetidine treatment in rats increases estrogen receptor-beta (ERbeta) in germ cells, correlating with apoptosis. This suggests ERbeta may play a role in cimetidine-induced germ cell death and hormonal disruption.
Area of Science:
- Reproductive Endocrinology
- Toxicology
Background:
- Cimetidine, an antiandrogenic drug, alters male hormone levels, including testosterone and FSH.
- Testicular damage in rats treated with cimetidine involves germ cell loss and Sertoli cell apoptosis.
- Sertoli cells are crucial for converting testosterone to estrogen via aromatase.
Purpose of the Study:
- To investigate the immunoexpression of estrogen receptors-beta (ERbeta) in the germ cells of rats treated with cimetidine.
- To explore the relationship between ERbeta immunoreactivity and germ cell apoptosis in cimetidine-induced testicular damage.
Main Methods:
- Adult male rats were treated with cimetidine (50 mg/Kg) or saline.
- Immunohistochemistry was used to detect ERbeta expression.
- The TUNEL method was employed to identify apoptotic germ cells.
Main Results:
- Cimetidine treatment enhanced ERbeta immunostaining in the cytoplasm and/or nuclei of germ cells within damaged tubules.
- ERbeta immunoreactivity was also observed in the flagellum and residual bodies of late spermatids.
- TUNEL-labeling, indicating apoptosis, was frequently found in germ cells with increased ERbeta expression.
Conclusions:
- Estrogen's role in spermiogenesis is supported by ERbeta presence in spermatid structures.
- Cimetidine-induced ERbeta overexpression may stem from interference with androgenization or aromatase activity due to Sertoli cell damage.
- The correlation between ERbeta overexpression and apoptosis suggests ERbeta's involvement in germ cell death.
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