论文标题:Elevated Temperatures Cause Transposon-Associated DNA Damage in C. elegans Spermatocytes
作者:Nicole A. Kurhanewicz, Devin Dinwiddie, Zachary D. Bush, Diana E. Libuda
摘要:Sexually reproducing organisms use meiosis to generate haploid gametes and faithfully transmit their genome to the next generation. In comparison to oogenesis in many organisms, spermatogenesis is particularly sensitive to small temperature fluctuations, and spermatocytes must develop within a very narrow isotherm [1, 2, 3, 4]. Although failure to thermoregulate spermatogenetic tissue and prolonged exposure to elevated temperatures are linked to male infertility in several organisms, the mechanisms of temperature-induced male infertility have not been fully elucidated [5]. Here, we show that upon exposure to a brief 2°C temperature increase, Caenorhabditis elegans spermatocytes exhibit up to a 25-fold increase in double-strand DNA breaks (DSBs) throughout meiotic prophase I and a concurrent reduction in male fertility. We demonstrate that these heat-induced DSBs in spermatocytes are independent of the endonuclease SPO-11. Further, we find that the production of these heat-induced DSBs in spermatocytes correlate with heat-induced mobilization of Tc1/mariner transposable elements, which are known to cause DSBs and alter genome integrity [6, 7]. Moreover, we define the specific sequences and regions of the male genome that preferentially experience these heat-induced de novo Tc1 insertions. In contrast, oocytes do not exhibit changes in DSB formation or Tc1 transposon mobility upon temperature increases. Taken together, our data suggest spermatocytes are less tolerant of higher temperatures because of an inability to effectively repress the movement of specific mobile DNA elements that cause excessive DNA damage and genome alterations, which can impair fertility.
众所周知,人类的正常体温大约是37℃,而产生精子的最佳温度则低于人体正常体温,在32℃-35℃之间,研究表明,暴露在这一温度范围以上仅仅1℃,就会对男性的生育能力产生不利影响。
热激诱导男性不育的现象已经得到了广泛研究和认可,例如,热水泡浴、穿着过于紧身的裤子,以及长时间驾驶,都会导致局部过热,从而影响男性生育功能。然而,其背后的具体机制尚不完全清楚。
2020年10月15日,美国俄勒冈大学的研究人员在 Cell 子刊 Current Biology 杂志发表了题为:Elevated Temperatures Cause Transposon-Associated DNA Damage in C. elegans Spermatocytes 的研究论文。
这项研究表明,精子对高温的耐受性较差,短时间的热激处理,就会导致原本被抑制的转座子重新活跃,从而导致过度的DNA损伤和基因组改变,最终损害生育能力。