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精索静脉曲张大鼠实验模型中,自噬在精索静脉曲张切除术前、后生殖细胞中的作用。

Involvement of autophagy in germ cells in an experimental model of varicocele in rats before and after varicocelectomy.

作者信息

Arena Salvatore, Ieni Antonio, Cassaro Fabiola, D'Antoni Santi, Tuccari Giovanni, Impellizzeri Pietro, Romeo Carmelo

机构信息

Unit of Pediatric Surgery, Department of Human Pathology of Adult and Childhood "Gaetano Barresi", University of Messina, 98121, Messina, Italy.

Unit of Human Pathology, Department of Human Pathology of Adult and Childhood "Gaetano Barresi", University of Messina, 98121, Messina, Italy.

出版信息

Pediatr Surg Int. 2024 Dec 18;41(1):31. doi: 10.1007/s00383-024-05913-8.

DOI:10.1007/s00383-024-05913-8
PMID:39694891
Abstract

INTRODUCTION

Autophagy, a catabolic process enabling cellular organelles and proteins' reuse for energy, has been observed in varicocele models, but the effect of surgical treatment on this process remains unknown. This study aims to assess autophagy in varicocele models undergoing surgical correction.

MATERIALS AND METHODS

Twenty-one adolescent male rats were induced with varicocele and divided into three groups: sham, varicocele, and varicocele with varicocelectomy. After 21 days, testicles were examined histologically for spermatogenesis (Jonhsen's score) and immunohistochemically for autophagy markers (LC3A, Beclin-1, Ambra-1, ULK-1, p62). Positive germ cells were quantitatively evaluated, and data were statistically analyzed (p < 0.05).

RESULTS

Histological examination revealed significantly reduced Jonhsen's scores in varicocele compared to sham and varicocelectomy groups (p < 0.05). Expression of autophagy markers (LC3A, Beclin-1, Ambra-1, ULK-1, p62) was significantly higher in varicocele than sham and varicocelectomy groups (p < 0.05), and in varicocelectomy than sham (p < 0.05).

CONCLUSIONS

Varicocele activates autophagy markers, with p62 potentially modulating autophagy despite being considered an inhibitor. While varicocelectomy improves histology, it doesn't fully inhibit autophagy, suggesting ongoing germ cell dysfunction despite treatment. This underscores varicocele's detrimental effects on germ cell functionality.

摘要

引言

自噬是一种分解代谢过程,可使细胞器和蛋白质得以再利用以获取能量,在精索静脉曲张模型中已观察到自噬现象,但手术治疗对这一过程的影响尚不清楚。本研究旨在评估接受手术矫正的精索静脉曲张模型中的自噬情况。

材料与方法

21只青春期雄性大鼠被诱导形成精索静脉曲张,并分为三组:假手术组、精索静脉曲张组和精索静脉曲张伴精索静脉结扎术组。21天后,对睾丸进行组织学检查以评估精子发生情况(约翰森评分),并通过免疫组织化学方法检测自噬标志物(LC3A、Beclin-1、Ambra-1、ULK-1、p62)。对阳性生殖细胞进行定量评估,并对数据进行统计学分析(p < 0.05)。

结果

组织学检查显示,与假手术组和精索静脉结扎术组相比,精索静脉曲张组的约翰森评分显著降低(p < 0.05)。精索静脉曲张组中自噬标志物(LC3A、Beclin-1、Ambra-1、ULK-1、p62)的表达明显高于假手术组和精索静脉结扎术组(p < 0.05),且精索静脉结扎术组高于假手术组(p < 0.05)。

结论

精索静脉曲张激活自噬标志物,尽管p62被认为是一种抑制剂,但它可能对自噬具有调节作用。虽然精索静脉结扎术改善了组织学情况,但并未完全抑制自噬,这表明尽管进行了治疗,生殖细胞功能仍持续存在障碍。这突出了精索静脉曲张对生殖细胞功能的有害影响。

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本文引用的文献

1
Stem Cell Factor Receptor Immunoexpression in Adolescent Varicocele.青春期精索静脉曲张中干细胞因子受体的免疫表达。
Urol J. 2020 Jun 23;17(4):391-396. doi: 10.22037/uj.v0i0.5351.
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Regulation of selective autophagy: the p62/SQSTM1 paradigm.选择性自噬的调控:p62/SQSTM1 范例。
Essays Biochem. 2017 Dec 12;61(6):609-624. doi: 10.1042/EBC20170035.
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Autophagy may play an important role in varicocele.自噬可能在精索静脉曲张中发挥重要作用。
Mol Med Rep. 2017 Oct;16(4):5471-5479. doi: 10.3892/mmr.2017.7253. Epub 2017 Aug 16.
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Varicocele and male infertility.精索静脉曲张与男性不育。
Nat Rev Urol. 2017 Sep;14(9):523-533. doi: 10.1038/nrurol.2017.98. Epub 2017 Jul 4.
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LC3/GABARAP family proteins: autophagy-(un)related functions.LC3/GABARAP家族蛋白:自噬相关(或非相关)功能
FASEB J. 2016 Dec;30(12):3961-3978. doi: 10.1096/fj.201600698R. Epub 2016 Sep 6.
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Clinical Outcomes of Varicocele Repair in Infertile Men: A Review.精索静脉曲张修复术治疗不育男性的临床结果:综述
World J Mens Health. 2016 Aug;34(2):101-9. doi: 10.5534/wjmh.2016.34.2.101. Epub 2016 Aug 23.
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Ambra1 in autophagy and apoptosis: Implications for cell survival and chemotherapy resistance.自噬与凋亡中的Ambra1:对细胞存活和化疗耐药性的影响
Oncol Lett. 2016 Jul;12(1):367-374. doi: 10.3892/ol.2016.4644. Epub 2016 May 30.
8
Varicocele and male infertility: current concepts and future perspectives.精索静脉曲张与男性不育:当前概念与未来展望
Asian J Androl. 2016 Mar-Apr;18(2):161-2. doi: 10.4103/1008-682X.172819.
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Novel insights into the pathophysiology of varicocele and its association with reactive oxygen species and sperm DNA fragmentation.精索静脉曲张的病理生理学及其与活性氧和精子DNA碎片关系的新见解。
Asian J Androl. 2016 Mar-Apr;18(2):186-93. doi: 10.4103/1008-682X.170441.
10
Role of Inhibitors of Apoptosis Proteins in Testicular Function and Male Fertility: Effects of Polydeoxyribonucleotide Administration in Experimental Varicocele.凋亡抑制蛋白在睾丸功能和男性生育中的作用:聚脱氧核糖核苷酸给药对实验性精索静脉曲张的影响
Biomed Res Int. 2015;2015:248976. doi: 10.1155/2015/248976. Epub 2015 Aug 4.