Carnitine Diminishes Etoposide Toxic Action on Spermatogonial Self-renewal and Sperm Production in Adult Rats Treated in the Prepubertal Phase

J Histochem Cytochem. 2020 May;68(5):327-342. doi: 10.1369/0022155420916274. Epub 2020 Mar 31.

Abstract

The aim of this study was to investigate carnitine action against negative effects of etoposide on stem/progenitor spermatogonia and on sperm production. Carnitine (250 mg/kg body weight/day) and etoposide (5 mg/kg body weight/day) were administered from 25-days postpartum to 32-days postpartum. Testes were collected at 32-days postpartum, 64-days postpartum, and 127-days postpartum, and submitted to the immuno-labeling of UTF1, SOX2, and PLZF proteins to identify undifferentiated spermatogonia populations. At 127-days postpartum, sperm were collected for analysis. Carnitine+etoposide group showed a higher numerical density of spermatogonia labeled for all studied proteins at 64-days postpartum (critical age) compared to the etoposide group. Moreover, there was an improvement of spermatic parameters and sperm DNA integrity in rats of the carnitine+etoposide group in comparison with rats of the etoposide group. The results suggest that carnitine improves the self-renewal of undifferentiated spermatogonia and promotes a partial protection on them, alleviating the etoposide harmful late effects and leading to an enhancement of the sperm parameters in adulthood.

Keywords: DNA integrity; cancer; carnitine; cell protector; chemotherapeutic agent; etoposide; pre-puberty; sperm; spermatogonia stem cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carnitine / pharmacology*
  • Cell Self Renewal / drug effects*
  • DNA Damage
  • Dose-Response Relationship, Drug
  • Etoposide / toxicity*
  • Male
  • Organ Size / drug effects
  • Promyelocytic Leukemia Zinc Finger Protein / metabolism
  • Rats
  • SOXB1 Transcription Factors / metabolism
  • Seminiferous Epithelium / drug effects
  • Seminiferous Epithelium / growth & development
  • Spermatogenesis / drug effects
  • Spermatogonia / cytology*
  • Spermatogonia / drug effects*
  • Spermatogonia / metabolism
  • Testis / drug effects
  • Testis / growth & development
  • Transcription Factors / metabolism

Substances

  • Promyelocytic Leukemia Zinc Finger Protein
  • SOXB1 Transcription Factors
  • Sox2 protein, rat
  • Transcription Factors
  • UTF1 protein, rat
  • Etoposide
  • Carnitine