Enhanced ERbeta immunoexpression and apoptosis in the germ cells of cimetidine-treated rats

Estela Sasso-Cerri1

  • 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

Abstract

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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