Testicular heat stress, a historical perspective and two postulates for why male germ cells are heat sensitive

Abstract

Herein, we compare the different experimental regimes used to induce testicular heat stress and summarise their impact on sperm production and male fertility. Irrespective of the protocol used, scrotal heat stress causes loss of sperm production. This is first seen 1-2 weeks post heat stress, peaking 4-5 weeks thereafter. The higher the temperature, or the longer the duration of heat, the more pronounced germ cell loss becomes, within extreme cases this leads to azoospermia. The second, and often underappreciated impact of testicular hyperthermia is the production of poor-quality spermatozoa. Typically, those cells that survive hyperthermia develop into morphologically abnormal and poorly motile spermatozoa. While both apoptotic and non-apoptotic pathways are known to contribute to hyperthermic germ cell loss, the mechanisms leading to formation of poor-quality sperm remain unclear. Mechanistically, it is unlikely that testicular hyperthermia affects messenger RNA (mRNA) abundance, as a comparison of four different mammalian studies shows no consistent single gene changes. Using available evidence, we propose two novel models to explain how testicular hyperthermia impairs sperm formation. Our first model suggests aberrant alternative splicing, while the second model proposes a loss of RNA repression. Importantly, neither model requires consistent changes in RNA species.

Effect of testicular degeneration on expression of sperm protein at 22 kDa in stallions

“…This technique was found to be effective in rams, 16–19 bulls, 20–23 stallions, 12 and boars 24,25 . The effect of heat exposure on the testes is dependent on temperature and duration 26 . We insulated the testes for 14 days, which is longer than previously reported by Freiedman et al 12 .…”

“…24,25 The effect of heat exposure on the testes is dependent on temperature and duration. 26 We insulated the testes for 14 days, which is longer than previously reported by Freiedman et al 12 While specially designed leather cups with straps and wool ensure an effective insulation system that does not allow air leakage 12 the diapers and cotton did allow some leakage of air, with the necessity of daily repairs, and this technique required extended duration to cause desired insult to the testes. A disadvantage to scrotal insulation is that the actual exposure temperature cannot be precisely controlled as with other techniques.…”

“…The testes are highly sensitive to heat stress, resulting in a loss or dysfunctional sperm production but the mechanism that leads to abnormal sperm morphology and function is not fully understood at a molecular and gene regulatory level. 26 Heating testicles increases the permeability of plasma membranes and lysosomes of germinal cells shown by leakage of cellular contents and increased staining with trypan blue. 29,30 This could explain the changes in the pattern(s) of SP22 on the spermatozoa from the treated testes/ epididymides.…”

Advancements in Genetic Biomarkers and Exogenous Antioxidant Supplementation for Safeguarding Mammalian Cells against Heat-Induced Oxidative Stress and Apoptosis

“…In the context of male reproductive cells, recent investigations have extensively explored the impact of heat stress on testis morphology, antioxidant status, and testicular biosynthesis [ 34 , 99 , 100 , 101 ]. Sertoli cells, known for providing structural and nutritional support for developing germ cells, have been a focus of scrutiny, with studies comprehensively examining the repercussions of heat stress on male reproductive cells, including Sertoli cells, spermatogonial stem cells, and Leydig cells [ 102 ].…”

“…Furthermore, HS casts a shadow over the ensuing fertilization processes, as elucidated by recent investigations [ 23 , 24 , 25 ]. Recent scientific inquiries have accentuated the detrimental influence of HS on sperm quality across a spectrum of mammalian species, encompassing dogs [ 17 ], bulls [ 20 ], buffaloes [ 26 ], stallions [ 27 , 28 , 29 ], rabbits [ 30 ], pigs [ 31 ], goats [ 32 ], and human males [ 33 , 34 ]. Remarkably, a recurring theme in these studies underscores the adverse impact of HS-induced oxidative stress and apoptosis on the viability of Sertoli cells, spermatogonial stem cells, Leyding cells, spermatogenesis, and sperm quality [ 15 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ].…”