Implications of Sertoli cell induced germ cell apoptosis to testicular pathology

Abstract

After exposure to toxicants, degenerating germ cells represents the most common testicular histopathological alteration, regardless of the mechanism of toxicity. Therefore, deciphering the primary toxicant cellular target and mechanism of action can be extremely difficult. However, most testicular toxicants display a cell-specific and a stage-specific pattern of damage, which is the best evidence for identifying the primary cellular target (i.e. germ cell, Sertoli cell, peritubular myoid cell, or Leydig cell). Some toxicant-induced Sertoli cell injury presents with germ cell apoptosis occurring primarily in spermatocytes in rats in stages XI-XIV, I and II. Although some toxicants result in spermatid degeneration and apoptosis, it is still unclear if spermatid apoptosis is a result of Sertoli cell-selective apoptosis or a direct effect of toxicants on spermatids, therefore if this is seen as the earliest change, one cannot infer the mechanism of apoptosis. This review summarizes some of the distinguishing features of Sertoli cell-induced germ cell apoptosis and the associated mechanisms of cell death to provide the toxicologist observing similar cell death, with evidence about a potential mode of action.

Keywords:

• apoptosis
• germ cellsm Sertoli cell
• histopathology
• spermatocytes
• testis

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

The authors would like to thank Dr. Kim Boekelheide and Linnea Anderson for providing the histological image used in Table 1 of this manuscript and Drs. Bob Chapin and Diane Creasy for critical reading of the manuscript prior to submission.

Funding

Supported, in part, by grants from the National Institutes of Health (ES016591 & ES007784 to J.H.R) and The University of Texas at Austin's Center for Molecular and Cellular Toxicology.