Heat stroke
Why overheating of the testicles leads to infertility
Anastasia Gorshkova, PCR.news
The testicles of most mammals are cooled in the scrotum, as a higher temperature leads to a violation of spermatogenesis and male infertility. A research team from Japan described this process in detail on an ex vivo cultured organ and found that at different temperatures, spermatogenesis is disrupted at different stages.
Previously, in order to investigate disorders of spermatogenesis due to an increase in testicular temperature in animal models, testicles were surgically moved into the abdominal cavity (artificial cryptorchidism). However, in such an experiment, it is impossible to control the exact temperature of the testes, as well as to vary it. In 2011, the same Japanese authors described a method for cultivating mouse testicles in an incubator.
The new study used transgenic mice in which the expression of the green fluorescent protein GFP was activated during meiotic prophase I under the promoter of acrosine, an enzyme that is released from the apical body of the sperm and participates in penetration through the egg shell. It turns out that GFP expression begins in pachytene spermatocytes (at the longest stage of the first division during spermatogenesis) and continues at subsequent stages of meiosis. The testes were cultured for five weeks at a temperature of 30-40 ° C, replacing the medium weekly, and at the end of the experiment, microscopy of the samples was performed.
Normal spermatogenesis in the scrotum (34 ° C) and impaired spermatogenesis in the abdominal cavity (38 ° C). Credit: NIBB, Japan
It turned out that spermatogenesis is disrupted at completely different stages under different conditions. At 38°C (the internal temperature of the mouse body), violations are observed at meiotic prophase I — the number of double-stranded DNA breaks increases, and the process of their repair is disrupted. Such damaged spermatocytes are destroyed by apoptosis at the control point of meiosis. At 37 °C, some spermatocytes survive to the late pachytene stage, maintaining high levels of double-stranded breaks, but they complete meiosis with a violation of the crossing processes. In the first case, spermatogenesis did not proceed further than early spermatocytes, in the second — further than late spermatocytes.
Unexpectedly, the most serious defect that was observed during testicular transplantation into the body cavity — blocking the transition from undifferentiated to differentiating spermatogonia — did not occur ex vivo at any temperature. This means that the pathology of cryptorchidism cannot be the result of overheating alone.
Thus, scientists have not only demonstrated the detrimental effect of high temperatures on spermatogenesis, but also discovered its temperature dependence. The key issues of future research are the molecular mechanism of thermal sensitivity and the biological significance of low temperatures for spermatogenesis.
Article by Hirano et al. Temperature sensitivity of DNA double-strand break repair underpins heat-induced meiotic failure in mouse spermatogenesis is published in the journal Communications Biology.
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