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全身热暴露导致雄性生殖细胞发育阶段特异性凋亡。

Whole-body heat exposure causes developmental stage-specific apoptosis of male germ cells.

机构信息

Department of Biological Sciences, Seoul National University, Seoul, Korea.

出版信息

Mol Reprod Dev. 2020 Jun;87(6):680-691. doi: 10.1002/mrd.23348. Epub 2020 Jun 7.

DOI:10.1002/mrd.23348
PMID:32506506
Abstract

Humans are occasionally exposed to extreme environmental heat for a prolonged period of time. Here, we investigated testicular responses to whole-body heat exposure by placing mice in a warm chamber. Among the examined tissues, the testis was found to be most susceptible to heat stress. Heat stress induces direct responses within germ cells, such as eukaryotic initiation factor 2α phosphorylation and stress granule (SG) formation. Prolonged heat stress (42°C for 6 hr) also disturbed tissue organization, such as through blood-testis barrier (BTB) leakage. Germ cell apoptosis was induced by heat stress for 6 hr in a cell type- and developmental stage-specific manner. We previously showed that spermatocytes in the early tubular stages (I-VI) form SGs for protection against heat stress. In the mid-tubular stages (VII-VIII), BTB leakage synergistically enhances the adverse effects of heat stress on pachytene spermatocyte apoptosis. In the late tubular stages (IX-XII), SGs are not formed and severe leakage of the BTB does not occur, resulting in mild apoptosis of late-pachytene spermatocytes near meiosis. Our results revealed that multiple stress responses are involved in germ cell damage resulting from prolonged heat stress (42°C for 6 hr).

摘要

人类偶尔会长时间暴露在极端环境热中。在这里,我们通过将小鼠置于温暖的室中来研究全身热暴露对睾丸的反应。在所检查的组织中,睾丸被发现对热应激最敏感。热应激会在生殖细胞内引起直接反应,例如真核起始因子 2α 的磷酸化和应激颗粒 (SG) 的形成。长时间的热应激(42°C 持续 6 小时)也会扰乱组织的结构,例如血睾屏障 (BTB) 的渗漏。热应激会以细胞类型和发育阶段特异性的方式诱导生精细胞凋亡 6 小时。我们之前曾表明,早期小管阶段(I-VI)的精母细胞会形成 SG 以抵御热应激。在中小管阶段(VII-VIII),BTB 渗漏协同增强了热应激对粗线期精母细胞凋亡的不利影响。在晚期小管阶段(IX-XII),不会形成 SG,BTB 也不会严重渗漏,导致接近减数分裂的晚期粗线期精母细胞发生轻度凋亡。我们的结果表明,长时间的热应激(42°C 持续 6 小时)会导致生殖细胞损伤,涉及多种应激反应。

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