The Effects of l-Carnitine Against Cyclophosphamide-Induced Injuries in Mouse Testis

Basic Clin Pharmacol Toxicol. 2017 Feb;120(2):152-158. doi: 10.1111/bcpt.12679. Epub 2016 Nov 4.

Abstract

In order to explore the possibility of l-carnitine (LC) as a protector of male fertility in chemotherapy, we observed the damage of cyclophosphamide (CTX) to Sertoli cells and the protective effect of LC on the testis Sertoli cells from such damage in this study. Healthy adult male mice were divided into three groups: chemotherapy group were injected intraperitoneally with the CTX; protective agent group were injected both LC and CTX; control group mice were injected only with isochoric physiological saline; all once a day for 5 days. After 5 days, the mice were, respectively, killed at 24 hr after the last injection. The testis and epididymis were removed. Epididymis was for sperm analysis immediately, and immunohistochemistry, RT-PCR and Western blot for the assessments of occludin, glial cell-derived neurotrophic factor (GDNF) and TGF-β3 mRNA and protein expression. The sperm analysis of epididymis showed that CTX can significantly decrease sperm count and motility; and administration of LC resulted in significant recovery of the sperm count and sperm motility. Compared with control group, the expressions of occludin and GDNF decreased and the expression of TGF-β3 increased significantly (p < 0.05) in the CTX group. In the LC + CTX group, the expressions of occludin and GDNF were higher than those of the CTX group and similar to those of the control group; the TGF-β3 expression was lower (p < 0.05) than that of the CTX group and similar to that of the control group. The results of this study showed that CTX could damage the spermatogenesis and reduce the expression of occludin and GDNF, and increase the expression of TGF-β3 in testis of mouse, which indicates CTX's damage or efficacy to testis Sertoli cells. LC could protect the Sertoli cells of testis from these damages caused by CTX, and promote or protect the spermatogenesis. In conclusion, this study provides meaningful information about the possible damage to male fertility by chemotherapeutics and potential of LC in the protection of male fertility during chemotherapy.

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / toxicity*
  • Blotting, Western
  • Carnitine / pharmacology*
  • Cell Survival / drug effects
  • Cyclophosphamide / toxicity*
  • Cytoprotection
  • Epididymis / drug effects
  • Epididymis / metabolism
  • Epididymis / pathology
  • Epididymis / physiopathology
  • Fertility / drug effects
  • Glial Cell Line-Derived Neurotrophic Factor / genetics
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism
  • Immunohistochemistry
  • Infertility, Male / chemically induced
  • Infertility, Male / pathology
  • Infertility, Male / physiopathology
  • Infertility, Male / prevention & control*
  • Male
  • Mice
  • Occludin / genetics
  • Occludin / metabolism
  • Polymerase Chain Reaction
  • Protective Agents / pharmacology*
  • Sertoli Cells / drug effects
  • Sertoli Cells / metabolism
  • Sertoli Cells / pathology
  • Sperm Count
  • Sperm Motility / drug effects
  • Spermatogenesis / drug effects
  • Spermatozoa / drug effects
  • Spermatozoa / metabolism
  • Spermatozoa / pathology
  • Testis / drug effects*
  • Testis / metabolism
  • Testis / pathology
  • Testis / physiopathology
  • Transforming Growth Factor beta3 / genetics
  • Transforming Growth Factor beta3 / metabolism

Substances

  • Antineoplastic Agents, Alkylating
  • Gdnf protein, mouse
  • Glial Cell Line-Derived Neurotrophic Factor
  • Occludin
  • Ocln protein, mouse
  • Protective Agents
  • Tgfb3 protein, mouse
  • Transforming Growth Factor beta3
  • Cyclophosphamide
  • Carnitine