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甲氨蝶呤可诱导大鼠生殖细胞凋亡并损害精子发生。

Methotrexate induces germ cell apoptosis and impairs spermatogenesis in a rat.

作者信息

Sukhotnik Igor, Nativ Omri, Roitburt Alex, Bejar Daniel, Coran Arnold G, Mogilner Jorge G, Nativ Ofer

机构信息

The Bruce Rappaport Faculty of Medicine, Laboratory of Intestinal Adaptation and Recovery, Technion-Israel Institute of Technology, Haifa, Israel.

出版信息

Pediatr Surg Int. 2013 Feb;29(2):179-84. doi: 10.1007/s00383-012-3197-0.

DOI:10.1007/s00383-012-3197-0
PMID:23224566
Abstract

PURPOSE

The primary toxic effects of methotrexate (MTX) are myelosuppression and/or intestinal mucositis. The objective of the present study is to investigate the effect of MTX on germ cell apoptosis and spermatogenesis in a rat.

METHODS

Male Sprague-Dawley rats were divided into three experimental groups: control rats treated with vehicle; MTX-2 rats treated with one dose (20 μg/kg) of MTX given IP and killed on the second day; and MTX rats treated with IP MTX (20 μg/kg) and killed on day 4. Johnsen's criteria and the number of germinal cell layers in the testes were used to categorize the spermatogenesis. TUNEL assay was used to determine germ cell apoptosis. Western blotting was used to determine Bax and Bcl-2 protein levels. Statistical analysis was performed using the non-parametric Kruskal-Wallis ANOVA test, with p less than 0.05 considered statistically significant.

RESULTS

On day 2, MTX-treated animals demonstrated minimal changes in the histological parameters of spermatogenesis, but germ cell apoptosis increased significantly (threefold increase, p = 0.002) compared to control rats. On day 4, MTX-treated rats demonstrated a trend toward a decrease in germ cell apoptosis, compared to day 2, and showed histological signs of impaired spermatogenesis (decreased number of germ cell layers and Johnsen's criteria). A significant increase in cell apoptosis in MTX-treated rats was correlated with higher Bax/Bcl-2 protein levels.

CONCLUSIONS

MTX induced germ cell apoptosis and impaired spermatogenesis in rat testes.

摘要

目的

甲氨蝶呤（MTX）的主要毒性作用是骨髓抑制和/或肠道黏膜炎。本研究的目的是探讨MTX对大鼠生殖细胞凋亡和精子发生的影响。

方法

将雄性Sprague-Dawley大鼠分为三个实验组：用赋形剂处理的对照大鼠；腹腔注射一剂MTX（20μg/kg）并在第二天处死的MTX-2大鼠；腹腔注射MTX（20μg/kg）并在第4天处死的MTX大鼠。采用约翰森标准和睾丸中生发细胞层数量对精子发生进行分类。TUNEL法用于测定生殖细胞凋亡。蛋白质免疫印迹法用于测定Bax和Bcl-2蛋白水平。采用非参数Kruskal-Wallis方差分析进行统计分析，p小于0.05被认为具有统计学意义。

结果

在第2天，MTX处理的动物精子发生的组织学参数变化最小，但与对照大鼠相比，生殖细胞凋亡显著增加（增加了三倍，p = 0.002）。在第4天，与第2天相比，MTX处理的大鼠生殖细胞凋亡呈下降趋势，并出现精子发生受损的组织学迹象（生发细胞层数减少和约翰森标准降低）。MTX处理的大鼠细胞凋亡显著增加与更高的Bax/Bcl-2蛋白水平相关。

结论

MTX诱导大鼠睾丸生殖细胞凋亡并损害精子发生。

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Environ Toxicol Pharmacol. 2011 Jan;31(1):143-52. doi: 10.1016/j.etap.2010.10.001. Epub 2010 Oct 28.
2
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Fertil Steril. 2009 Oct;92(4):1466-1469. doi: 10.1016/j.fertnstert.2009.04.026. Epub 2009 May 29.
3
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Clin Exp Reprod Med. 2021 Sep;48(3):211-220. doi: 10.5653/cerm.2020.04105. Epub 2021 Jul 20.
4
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Integr Cancer Ther. 2020 Jan-Dec;19:1534735420969814. doi: 10.1177/1534735420969814.
5
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6
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7
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4
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Mol Hum Reprod. 2003 Apr;9(4):219-25. doi: 10.1093/molehr/gag031.
5
Balance of apoptosis and proliferation of germ cells related to spermatogenesis in aged men.老年男性中与精子发生相关的生殖细胞凋亡与增殖的平衡
J Androl. 2003 Mar-Apr;24(2):185-91. doi: 10.1002/j.1939-4640.2003.tb02661.x.
6
Germ cell apoptosis in undescended testis: the origin of its impaired spermatogenesis in the TS inbred rat.隐睾中生殖细胞凋亡：TS近交系大鼠睾丸生精功能受损的起源
J Urol. 2002 Jul;168(1):343-7.
7
Fertility and unilateral undescended testis in the rat model III: ultrastructural changes in the contralateral descended testis.大鼠模型中的生育力与单侧隐睾 III：对侧下降睾丸的超微结构变化
Pediatr Surg Int. 2002 May;18(4):276-80. doi: 10.1007/s003830100684.
8
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Hum Reprod Update. 2001 Sep-Oct;7(5):461-72. doi: 10.1093/humupd/7.5.461.
9
The effect of drugs and toxins on the process of apoptosis.药物和毒素对细胞凋亡过程的影响。
Drug Metabol Drug Interact. 2001;18(1):1-32. doi: 10.1515/dmdi.2001.18.1.1.
10
Germ cell suicide: new insights into apoptosis during spermatogenesis.生殖细胞自杀：精子发生过程中细胞凋亡的新见解。
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