28 October 2020

Keep your testicles in the cold

High temperature damaged the DNA of spermatocytes

Natalia Miranda, N+1

American scientists, when heating Caenorhabditis elegans nematodes, found a significant increase in the frequency of DNA damage in their spermatocytes – this was associated with the active mobilization of Tc1/mariner transposons. At the same time, no similar processes were observed in female gametes, as the authors write in the journal Current Biology (Kurhanewicz et al., Elevated Temperatures Cause Transposon-Associated DNA Damage in C.elegans Spermatocytes).

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Drawings from an article in Current Biology.

In many organisms, spermatogenesis, unlike the formation of female gametes, is extremely dependent on fluctuations in ambient temperature, and for the maturation of spermatocytes, it is necessary that the process proceeds in a narrow temperature range. Despite the fact that this is also true for humans, and temperature-dependent disorders of spermatogenesis are associated with disorders of male reproductive function, the molecular mechanisms underlying this are still poorly understood.

Diana E. Libuda, together with colleagues from the University of Oregon, shed light on this problem by studying changes in the hereditary apparatus of C.elegans gametes subjected to heat shock. Spermatogenesis was studied on males, oogenesis – on hermaphrodites. Animals of the experimental group were heated to 34 degrees Celsius for two hours, the temperature of the medium was not increased for the control group, and to measure the degree of DNA damage, the researchers compared the number of RAD-51 recombinase foci in gametes – areas of the nucleus where recombinase forms complexes with DNA at the site of a double-stranded break for its repair. It turned out that the number of RAD-51 foci in prophase I of meiosis significantly increased in spermatocytes subjected to heat shock (41±17 foci/nucleus versus 1.6±2.7 foci per nucleus in non-heated spermatocytes; p<0.0001). At the same time, nothing like this was observed in oocytes.

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Immunofluorescence analysis of C.elegans spermatocytes and oocytes after heating and control group. DNA is shown in blue, and RAD–51 recombinase foci are shown in green (x is the average number of foci per nucleus).

To make sure that DNA disorders affect male fertility, scientists obtained offspring from individuals subjected and not subjected to heat shock. It is noteworthy that the ability to fertilize spermatocytes was not impaired – the researchers received a comparable number of eggs from individuals of the control and experimental groups. However, if there was no noticeable quantitative difference, the qualitative one turned out to be very significant: the number of non-viable eggs from males subjected to heat shock (on average 6±4 dead eggs/brood; the number of broods is 38) is on average three times more (p<0.001) than from males of the control group (on average 2±2 dead eggs/brood; number of broods 23).

The authors suggested that the cause of the violation of the integrity of the genetic apparatus of male gametes may be the mobilization of transposons, which leads to the appearance of double-stranded breaks in DNA. They checked using quantitative PCR analysis by analyzing the expression level of Tc1 transposase. It turned out that the expression of Tc1-transposase in heated C.elegans was 2.4 times higher than in the control group, while no significant difference was found in oocytes. However, the authors note that a 2.4-fold increase in the expression of the Tc1 transposase gene hardly explains the 25-fold increase in DNA damage in spermatocytes, therefore, they clarify that the mobilization of Tc1/mariner transposons is probably only one of the reasons for the violation of the genetic apparatus of male C.elegans gametes when exposed to high temperatures.

The study opens up the potential for a deep understanding of the processes associated with disorders of spermatogenesis in various organisms when the temperature of the environment changes. In addition, it allows us to speculate about the presence of certain mechanisms that suppress these pathological processes in female gametes – also a promising subject for study.

Fertility issues, including male ones, are being studied quite actively. For example, epigenetic factors that arise due to stress and affect the quality of sperm are already known. But if it is not so easy to cope with chronic stress, then it is easier to give preference to a certain type of underwear and, apparently, it makes sense, because men in boxers tend to have healthier sperm.

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