Mechanisms of toxic damage to spermatogenesis

J Natl Cancer Inst Monogr. 2005;(34):6-8. doi: 10.1093/jncimonographs/lgi006.

Abstract

Azoospermia and long-lasting testicular atrophy are common adverse consequences of cancer treatment. Chemotherapeutic agents may disrupt spermatogenesis by targeting various testicular cell types (Leydig cells, Sertoli cells, and germ cells) and by activating numerous molecular pathways involved in germ cell life-and-death decision making. Genetically modified animal models with deficiencies in specific proapoptotic and prosurvival pathways have become powerful tools in understanding the molecular regulation of spermatogenesis and the response of the seminiferous epithelium to toxic injury. In this brief review, selected examples of results of toxic exposures in genetically deficient animal models are discussed to highlight the roles of p53 and the Fas system as modulators of proapoptotic activity in the testis. A final section focuses on cisplatin, a cancer chemotherapeutic agent that produces male reproductive toxicity by targeting multiple cell types in the testis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis
  • Cisplatin / adverse effects
  • Cisplatin / therapeutic use
  • Genes, p53
  • Humans
  • Male
  • Oligospermia / chemically induced*
  • Receptors, Tumor Necrosis Factor / genetics
  • Risk Factors
  • Spermatogenesis / drug effects*
  • Testis / drug effects
  • Testis / pathology
  • fas Receptor

Substances

  • Antineoplastic Agents
  • FAS protein, human
  • Receptors, Tumor Necrosis Factor
  • fas Receptor
  • Cisplatin