Experimental mild increase in testicular temperature has drastic, but reversible, effect on sperm aneuploidy in men: A pilot study

Abstract

In mammals testicular and epididymal temperature increase impairs spermatogenesis. This experimental study investigates the effects of a mild testis temperature increase (i.e. testis temperature remains below core body temperature) on sperm aneuploidy in men. In 5 fertile volunteers a testicular temperature increase was induced by maintaining the testes at suprascrotal position using specially designed underwear for 15 ± 1 h daily for 120 consecutive days. After heating men were followed for next 180 days. A control group (27 men) was recruited. Semen samples were collected before, during and after heating period and analyzed for chromosomes X, Y and 18 for aneuploidy using FISH. A total of 234,038 spermatozoa were studied by FISH. At day 34 of heating, mean sperm aneuploidy values were not modified. From day 34 of heating until day 45 post heating, FISH evaluation was not possible due to the drastic fall of sperm count. At day 45 post-heating total sperm aneuploidy percentage was twice higher than before heating whereas. Sex disomy (sperm XY18), sex chromosome nullisomy (sperm 18) were significantly higher than controls. These effects were completely reversed at 180 days post heat exposure. Conclusion: A mild rise in testicular temperature significantly increases sperm aneuploidies, reflecting an effect on the meiosis stage of spermatogenesis. The effect of heating was reversible and suggests that recovery of aneuploidy to normal values requires at least two cycles of spermatogenesis. Nonetheless, the low number of volunteers was a limitation of this pilot study and warrants further research on larger population.

Introduction

The adverse effects of increased testicular temperature on spermatogenesis in mammals have been investigated and established for many years. In most mammals, testes are located in the scrotum outside the body, which provides anatomical location that offers lower testicular temperature than core body. In a thermoneutral environment, the scrotal testes are appreciably cooler than the body, but this does not mean that they are kept at a constantly lower temperature [1]. In man as in most other mammals, optimal spermatogenesis requires 2–6 °C lower testicular temperature than body and any rise above the physiological temperature of the testes has adverse impact on spermatogenesis [2,3].

Several pathological conditions are associated with an increase in testicular temperature which include cryptorchidism [4], varicocele [[5], [6], [7]] and febrile diseases [8,9]. Exogenous factors such as occupational exposure to high temperatures [10,11], car driving [12] or sauna exposure [[13], [14], [15]] also increase the testicular temperature. Notably, some living conditions such as wearing tight clothing [16] or sitting and sleeping postures [17] are also associated with an increase in testicular temperature which remains in the physiological range [18]. The relation between lifestyle factors or exposure to environmental risk factors and sperm aneuploidy was investigated in several studies [[19], [20], [21], [22]], but to our knowledge, only one epidemiological study has reported the possible link between circumstances known to improve testicular temperature, such as sauna use or type of underwear, and sperm aneuploidy and have shown decrease in sperm aneuploidy in men wearing boxer shorts compared to those wearing tight underwear [23].

In man, different experimentally methods increasing testicular temperature resulted in a drastic, but reversible, inhibition of spermatogenesis with decrease in sperm count [13,[24], [25], [26], [27], [28]] sperm motility [13,[24], [25], [26], [27]] and sperm normal morphology [13,25,26]. In addition to conventional sperm parameters (count, motility, morphology) the adverse effects of testicular hyperthermia on sperm DNA damage have also been reported [13,24].

It has been suggested that a modification of testicular temperature could be used in two ways: increasing testes temperature to inhibit spermatogenesis or decreasing it to improve spermatogenesis in infertile men who have abnormally elevated testes temperatures. Experimental studies [[29], [30], [31]] and reviews [[32], [33], [34]] have reported that a mild testis temperature increase could be used as a male contraceptive approach. On the other hand, reducing the testicular temperature using application of an ice bag for 30 min per day for 14 days improves spermatogenesis outcome [35]. Various devices have been used to decrease testicular temperature and improve spermatogenesis, either in varicocele or in oligozoospermic patients having higher scrotal temperatures [[36], [37], [38]]. In addition, avoidance of exposure to heat has been reported to prevent infertility [[39], [40], [41]].

We have previously demonstrated that a mild increase in testicular and epididymal temperature (+2 °C, i.e. a testicular temperature below core body temperature), induced by maintaining the testes in a suprascrotal position, had drastic effects not only on sperm output and quality but also on sperm DNA fragmentation in humans [24].

While a study in mice [42] reported X-Y dissociation increase in spermatocytes from animals that were exposed to an environmental temperature of 35 °C for 2–5 days (whole body exposure), to date no study has investigated the effect of a mild testicular temperature increase (testicular temperature below core temperature) on sperm aneuploidy in men. A recent study in man reported increased sperm aneuploidy after testicular exposure to 43 °C for two successive days per week for 3 months. [43]. Noteworthy, 43 °C is very high temperature compared to physiological temperature of testes (≈34.5 °C) and sperm aneuploidy is more likely to occur at this higher temperature threshold.

Sperm aneuploidy can be a risk to the embryonic and fetal development and the offspring [44,45]. The majority of the aneuploidy embryos are not viable resulting into miscarriages but several chromosomal abnormalities, such as autosomal trisomy or sex chromosome aneuploidy, could be non-lethal and compatible with survival resulting in birth and developmental defects [[44], [45], [46], [47]].

In this context, the objective of this study was to evaluate the effects of a mild testicular temperature increase (+2 °C) on sperm aneuploidy in fertile men and to examine its potential reversibility.