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TNF-α 及其靶标 HSP-70 在触发正常精子和非正常精子样本凋亡中的作用。

The Role of TNF-α and Its Target HSP-70 in Triggering Apoptosis in Normozoospermic and Non-Normozoospermic Samples.

机构信息

Department of Histology and Embryology, Istanbul Medipol University, School of Medicine, Istanbul, Turkey.

Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, Turkey.

出版信息

Biopreserv Biobank. 2022 Dec;20(6):485-492. doi: 10.1089/bio.2021.0056. Epub 2022 Jun 1.

Abstract

Semen analysis is performed as one of the screening tests for infertility, including motility, morphology, and concentration observation. We aimed to investigate the expression rates of tumor necrosis factor-α (TNF-α) and heat shock protein (HSP)-70 as two opposite affectors of apoptosis in men with normal semen parameters and abnormal parameters to find the possible effect of this pathway on sperm parameters. We also aimed to investigate the apoptotic markers (DNA fragmentation and Caspase-3 expression) to observe the correlation of this pathway with apoptosis. A total of 32 men who applied for infertility evaluation were included in the study. Semen analysis was performed according to WHO criteria. Liquefaction time, appearance, volume, pH, viscosity, sperm concentration, total motility rate, sperm motility, and percentage of spermatozoa with normal morphology were determined. TNF-α, HSP-70, and Caspase-3 immunolocalization were scored histologically. A sperm chromatin dispersion test was used to observe DNA fragmentation. There was no significant difference in TNF-α protein expression rate (mild level). The HSP-70 expression rate was lower, especially in the head region of normo. Caspase-3 was higher totally in non-normo. DNA fragmentation levels were similar in both the groups. From TNF-α protein expression at the mild level in both the groups, it may be hypothesized that the apoptotic pathway might not be triggered by the extrinsic pathway. We found a negative correlation between HSP-70 and Caspase-3 expressions, providing further evidence that HSP-70 works as an inhibitor to apoptosis. This, particularly on specific points, made us think the communication might begin in the anterior chamber, then flow through the cell body to the tail. HSP-70 expression was lower in normo than in non-normo, indicating the possible role of HSP-70 as an answer to any type of stressor in non-normozoospermic patients. Correspondingly, it may be concluded that HSP has an antiapoptotic effect, causing inhibition in the elimination of abnormal sperm cells impairing sperm parameters.

摘要

精液分析是不孕不育筛查测试之一,包括观察精子活力、形态和浓度。我们旨在研究具有正常精液参数和异常参数的男性中肿瘤坏死因子-α(TNF-α)和热休克蛋白(HSP)-70 两种相反凋亡效应物的表达率,以发现该途径对精子参数的可能影响。我们还旨在研究凋亡标志物(DNA 片段化和 Caspase-3 表达),以观察该途径与凋亡的相关性。

共有 32 名申请不孕评估的男性纳入研究。根据世界卫生组织(WHO)标准进行精液分析。确定液化时间、外观、体积、pH 值、粘度、精子浓度、总活力率、精子活力和正常形态精子百分比。组织学评分 TNF-α、HSP-70 和 Caspase-3 免疫定位。使用精子染色质扩散试验观察 DNA 片段化。TNF-α 蛋白表达率(轻度)无显著差异。HSP-70 表达率较低,尤其是在正常形态精子头部区域。非正常形态精子的 Caspase-3 总水平较高。两组的 DNA 片段化水平相似。

从两组的 TNF-α 蛋白表达轻度来看,可能假设凋亡途径可能不是由外在途径触发的。我们发现 HSP-70 和 Caspase-3 表达之间存在负相关,这进一步证明 HSP-70 作为凋亡的抑制剂起作用。这一点,特别是在特定的方面,使我们认为这种通讯可能始于前房,然后通过细胞体流向尾部。正常形态精子的 HSP-70 表达低于非正常形态精子,表明 HSP-70 可能作为非畸形精子症患者任何类型应激源的应答发挥作用。相应地,可以得出结论,HSP 具有抗凋亡作用,导致异常精子细胞的消除受到抑制,从而损害精子参数。

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