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睾丸转录组分析表明，克氏综合征患者支持细胞和间质细胞功能失调。

Deregulation of sertoli and leydig cells function in patients with Klinefelter syndrome as evidenced by testis transcriptome analysis.

作者信息

D'Aurora Marco, Ferlin Alberto, Di Nicola Marta, Garolla Andrea, De Toni Luca, Franchi Sara, Palka Giandomenico, Foresta Carlo, Stuppia Liborio, Gatta Valentina

机构信息

Department of Psychological, Humanities and Territorial Sciences, School of Medicine and Health Sciences, "G.d'Annunzio" University, Via Dei Vestini 31, 66100, Chieti-Pescara, Italy.

Functional Genetics Unit, Center of Excellence on Aging (Ce.S.I.), Via Dei Vestini 31, 66100, Chieti, Italy.

出版信息

BMC Genomics. 2015 Mar 7;16(1):156. doi: 10.1186/s12864-015-1356-0.

DOI:10.1186/s12864-015-1356-0
PMID:25879484
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4362638/
Abstract

BACKGROUND

Klinefelter Syndrome (KS) is the most common abnormality of sex chromosomes (47,XXY) and represents the first genetic cause of male infertility. Mechanisms leading to KS testis degeneration are still not completely defined but considered to be mainly the result of germ cells loss. In order to unravel the molecular basis of global testis dysfunction in KS patients, we performed a transcriptome analysis on testis biopsies obtained from 6 azoospermic non-mosaic KS patients and 3 control subjects.

RESULTS

The analysis found that, compared to controls, KS patients showed the differential up- and down-expression of 656 and 247 transcripts. The large majority of the deregulated transcripts were expressed by Sertoli cells (SCs) and Leydig cells (LCs). Functional analysis of the deregulated transcripts indicated changes of genes involved in cell death, inflammatory response, lipid metabolism, steroidogenesis, blood-testis-barrier formation and maintenance, as well as spermatogenesis failure.

CONCLUSIONS

Taken together, present data highlight the modulation of hundreds of genes in the somatic components of KS patient testis. The increased LCs steroidogenic function together with the impairment of inflammatory pathways and BTB structure, result in increased apoptosis. These findings may represent a critical roadmap for therapeutic intervention and prevention of KS-related testis failure.

摘要

背景

克兰费尔特综合征（KS）是最常见的性染色体异常疾病（47,XXY），是男性不育的首要遗传病因。导致KS患者睾丸退化的机制尚未完全明确，但主要被认为是生殖细胞丢失的结果。为了阐明KS患者睾丸整体功能障碍的分子基础，我们对6例无精子症非嵌合型KS患者和3例对照受试者的睾丸活检组织进行了转录组分析。

结果

分析发现，与对照组相比，KS患者有656个转录本上调表达，247个转录本下调表达。绝大多数失调的转录本由支持细胞（SCs）和间质细胞（LCs）表达。对失调转录本的功能分析表明，参与细胞死亡、炎症反应、脂质代谢、类固醇生成、血睾屏障形成和维持以及精子发生失败的基因发生了变化。

结论

综上所述，目前的数据突出了KS患者睾丸体细胞成分中数百个基因的调控情况。间质细胞类固醇生成功能增强，以及炎症途径和血睾屏障结构受损，导致细胞凋亡增加。这些发现可能为治疗干预和预防KS相关睾丸功能衰竭提供关键的路线图。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2535/4362638/aca42ced86d1/12864_2015_1356_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2535/4362638/eecb400cfd8b/12864_2015_1356_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2535/4362638/214313699e6f/12864_2015_1356_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2535/4362638/7820be06e98b/12864_2015_1356_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2535/4362638/aca42ced86d1/12864_2015_1356_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2535/4362638/eecb400cfd8b/12864_2015_1356_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2535/4362638/214313699e6f/12864_2015_1356_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2535/4362638/7820be06e98b/12864_2015_1356_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2535/4362638/aca42ced86d1/12864_2015_1356_Fig4_HTML.jpg

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