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Carnitine reduces testicular damage in rats treated with etoposide in the prepubertal phase

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Abstract

Etoposide is a chemotherapeutic agent that induces cell death by blocking topoisomerase II catalytic function. Although etoposide is effective in the treatment of cancer, it also causes the death of normal proliferating cells, including male germ cells. Administration of etoposide during the prepubertal phase causes diturbances in several testicular morphometric parameters and in Sertoli cells. Cytoprotection of the seminiferous epithelium is the only means of preserving potential male reproduction in prepubertal cancer patients. Carnitine, an amino acid naturally present in normal cells, is a promising cryoprotectant as it is concentrated in the epididymis and promotes sperm maturation. We have therefore investigated whether carnitine protects rat testes against etoposide and, thus, improves fertility in adulthood. Our results suggest that carnitine partially protects the testis against damage caused by etoposide, although the mechanism by which it happens remains unknown.

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Authors and Affiliations

  1. Laboratory of Developmental Biology, Federal University of Sao Paulo, 740 Botucatu, Ed. Leitao da Cunha (2nd floor), Sao Paulo, SP, Brazil, 04023-900

    Fatima Kazue Okada, Taiza Stumpp & Sandra Maria Miraglia

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  1. Fatima Kazue Okada
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  2. Taiza Stumpp
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  3. Sandra Maria Miraglia
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Correspondence to Fatima Kazue Okada.

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Fig. S1-S2

S1: Photomicrographs of rat testicular cross-sections of the Sham-control group submitted to PAS + H method. A: Seminiferous epithelium of a 32 day-old rat showing normal morphology of the seminiferous epithelium. Note the presence of type B spermatogonia (arrow) Inset: Detail of a type B spermatogonium. B: Sections of seminiferous tubules of a 64 day-old rat. The seminiferous epithelium shows normal morphology and step 19 spermatids are observed, indicating that spermiogenesis is complete. Inset: Detail of step 19 spermatids observed in the seminiferous epithelium of these rats. C: Seminiferous tubule section of an adult rat (127 day-old) showing normal morphology. Inset: Detail of step 19 spermatids observed in this seminiferous epithelium. S2: Photomicrographs of testicular cross-sections of Sham-control rats submitted to TUNEL-method. A: Sections of seminiferous tubules of a 32 day-old rat. Observe the TUNEL-positive cell located in the region generally occupied by the primary spermatocytes (arrow). B: Seminiferous tubule section of a 64 day-old rat showing a TUNEL-positive cell located near to the peritubular tissue (arrow). C: Seminiferous tubule section of a S127 rat showing TUNEL-positive cells located in the region generally occupied by spermatogonia (arrows) (TIFF 807 KB).

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Okada, F.K., Stumpp, T. & Miraglia, S.M. Carnitine reduces testicular damage in rats treated with etoposide in the prepubertal phase. Cell Tissue Res 337, 269–280 (2009). https://doi.org/10.1007/s00441-009-0801-2

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