Effects of exogenous testosterone on testicular function during the chronic phase of spinal cord injury: dose effects on spermatogenesis and Sertoli cell and sperm function.
BACKGROUND
Exogenous testosterone has been shown to attenuate spinal cord injury (SCI)-related regression of spermatogenesis in the rat. The current experiment investigated the effects of exogenous testosterone in testicular and sperm functions in the rat during the chronic phase of SCI.


METHODS
Chronic SCI rats were given subcutaneous implants of testosterone-filled silastic capsules (TC). Northern blot cDNA hybridization was used to measure testicular levels of Sertoli cell- and germ cell-specific transcripts. Western blot and immunohistochemistry were used to determine protein level and cellular localization, respectively, of cyclic adenosine monophosphate-responsive element modulator (CREM) in the testes. Flow cytometry was used to determine sperm viability and mitochondrial potential.


RESULTS
Spontaneous restoration of spermatogenesis occurred in 7 of the 8 untreated SCI rats. Although exogenous testosterone restored complete spermatogenesis in all SCI rats, regressed seminiferous epithelium remained in 30% to 70% of tubular cross sections in these rats. These effects were associated with altered responses of germ cell-specific mRNA transcripts to exogenous testosterone, and abnormal cellular distribution of CREM. Sperm of untreated SCI rats exhibited lowered motility, viability, and mitochondrial potential. Implantation of 10 cm of TC worsened sperm motility in sham control and SCI rats, but restored sperm viability and mitochondrial potential in SCI rats.


CONCLUSIONS
Administration of exogenous testosterone to SCI rats during the chronic phase of injury failed to facilitate spermatogenic restoration over that achieved in untreated SCI rats. Abnormalities in postmeiotic spermatogenic differentiation could contribute to these effects, and perhaps the production of sperm with abnormal morphology and/or functions during the chronic phase of SCI.
Huang
Hosea F S
HF
Veterans Affairs Medical Center, East Orange, New Jersey, USA. huanghf@umdnj.edu
Li
Ming-Tang
MT
Wang
Shulun
S
Barton
Beverly
B
Anesetti
Robert
R
Jetko
James A
JA
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002470:Cell Survival; D002908:Chronic Disease; D051786:Cyclic AMP Response Element Modulator; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D008564:Membrane Potentials; D008928:Mitochondria; D009693:Nucleic Acid Hybridization; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins; D012708:Sertoli Cells / Q000187:drug effects*; D013081:Sperm Motility; D013091:Spermatogenesis / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D013737:Testis / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D013739:Testosterone / Q000008:administration & dosage / Q000494:pharmacology*; D014018:Tissue Distribution
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D051786:Cyclic AMP Response Element Modulator; D013739:Testosterone