Hyperthermia is more important than hypoxia as a cause of disrupted spermatogenesis and abnormal sperm

We tested the hypothesis that hypoxia replicates effects of hyperthermia on reducing number and quality of sperm produced, whereas hyperoxia mitigates effects of hyperthermia. Forty-eight CD-1 mice (similar to 50 d old), inspired air with 13, 21, or 95% O-2 and were exposed to ambient temperatures of 20 or 36 degrees C (3 x 2 factorial, six groups) twice for 12 h (separated by 12 h at 20 degrees C and 21% O-2), with euthanasia 14 or 20 d after first exposure. Combined for both post-exposure intervals, there were primarily main effects of temperature; mice exposed to 20 vs 36 degrees C had differences in testis weight (110.2 vs 96.9 mg, respectively; P < 0.0001), daily sperm production (24.7 vs 21.1 x 10(6) sperm/g testes, P < 0.03), motile sperm (54.5 vs 41.5%, P < 0.002), morphologically normal sperm (59.9 vs 45.4%, P < 0.002), morphologically abnormal heads (7.3 vs 22.0%, P <0.0001), seminiferous tubule diameter (183.4 vs 176.3 mu m, P < 0.004) and altered elongated spermatids (2.2 vs 15.9, P < 0.001). Increasing O-2 (from 13 to 95%) affected morphologically abnormal heads (15.4, 10.8 and 17.6%, respectively; P < 0.03), seminiferous tubule diameter (175.7, 185.6 and 178.4 mu m, P < 0.003) and total altered spermatids (8.3, 3.3 and 15.2, P < 0.05). Our hypothesis was not supported; hypoxia did not replicate effects of hyperthermia with regards to reducing number and quality of sperm produced and hyperoxia did not mitigate effects of hyperthermia. We concluded that hyperthermia per se and not secondary hypoxia was the fundamental cause of heat-induced effects on spermatogenesis and sperm. These findings are of interest to develop evidence-based efforts to mitigate effects of testicular hyperthermia, as efforts should be focused on hyperthermia per se and not on hyperthermia-induced hypoxia. (C) 2019 Elsevier Inc. All rights reserved.