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Open Access Research

Late morfofunctional alterations of the Sertoli cell caused by doxorubicin administered to prepubertal rats

Otávio Brilhante1, Fatima K Okada2, Estela Sasso-Cerri3, Taiza Stumpp2* and Sandra M Miraglia2

Author Affiliations

1 Centre for Health and Rural Technology, Academic Unit of Veterinary Medicine, Federal University of Campina Grande, Patos, Paraíba, Brazil

2 Department of Morphology and Genetics, Developmental Biology Laboratory, Federal University of São Paulo. Vila Clementino, São Paulo, SP, Brazil

3 Department of Morphology, Laboratory of Histology and Embryology, Dental School of São Paulo State University (UNESP), Araraquara, SP, Brazil

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Reproductive Biology and Endocrinology 2012, 10:79  doi:10.1186/1477-7827-10-79

Published: 11 September 2012

Abstract

Background

Doxorubicin is a potent chemotherapeutic drug used against a variety of cancers. It acts through interaction with polymerases and topoisomerase II and free radical production. Doxorubicin activity is not specific to cancer cells and can also damage healthy cells, especially those undergoing rapid proliferation, such as spermatogonia. In previous studies our group showed that etoposide, another topoisomarese II poison, causes irreversible damage to Sertoli cells. Thus, the aim of this study was to address the effects of doxorubicin on Sertoli cell morphology and function and on the seminiferous epithelium cycle when administered to prepubertal rats.

Methods

Prepubertal rats received the dose of 5 mg/Kg of doxorubicin, which was fractioned in two doses: 3 mg/Kg at 15dpp and 2 mg/Kg at 22dpp. The testes were collected at 40, 64 and 127dpp, fixed in Bouin’s liquid and submitted to transferrin immunolabeling for Sertoli cell function analysis. Sertoli cell morphology and the frequency of the stages of the seminiferous epithelium cycle were analyzed in PAS + H-stained sections.

Results

The rats treated with doxorubicin showed reduction of transferrin labeling in the seminiferous epithelium at 40 and 64dpp, suggesting that Sertoli cell function is altered in these rats. All doxorubicin-treated rats showed sloughing and morphological alterations of Sertoli cells. The frequency of the stages of the seminiferous epithelium cycle was also affected in all doxorubicin-treated rats.

Conclusions and discussion

These data show that doxorubicin administration during prepuberty causes functional and morphological late damage to Sertoli cells; such damage is secondary to the germ cell primary injury and contributed to enhance the spermatogenic harm caused by this drug. However, additional studies are required to clarify if there is also a direct effect of doxorubicin on Sertoli cells producing a primary damage on these cells.

Keywords:
Doxorubicin; Sertoli cell; Spermatogenesis; Rat; Transferrin