Reversibility of Spermatogonial Stem Cell Injury After Single Acute Scrotal Hyperthermia in Mouse and Rat Models: A Systematic Review

Background: Acute scrotal hyperthermia is a recognized spermatogenesis stressor, but recovery of spermatogonial stem cells after a single mild heat exposure remains unclear, particularly over cycle-relevant timeframes. This systematic review evaluates the in vivo local scrotal hyperthermia across at least one full spermatogenic cycle. Methods: A PICO-driven search identified 18 mouse and rat studies using a single scrotal heating exposure. Outcomes were synthesized thematically across structural, cellular, endocrine/apoptotic, and sperm domains. Results: Injury patterns were graded and temperature- and species-dependent, with more consistent abnormalities at 43°C and milder effects in rats than in mice. Structural endpoints often remained abnormal at the longest follow-up, and architectural repair did not reliably achieve functional recovery. Mouse stereology at 43°C indicated long-term SSC and germ-cell depletion, with Leydig-cell and partial Sertoli-cell losses; rat stereology was sparse and absent at 42°C. Testosterone responses were heterogeneous, whereas tubular apoptosis was more consistently elevated in mice at 43°C. Sperm concentration/count declined where assessed, with more frequent impairments of motility and other quality indices, including DNA integrity, at 43°C. Conclusion: Recovery was often incomplete and endpoint-specific, with impairment more consistently detected at 43°C, particularly in mice. Future studies require standardized thermal dosing, transparent bias-mitigation, and SSC/niche-resolved functional assays.