Testicular microbiome in azoospermic men-first evidence of the impact of an altered microenvironment.

Testicular microbiome in azoospermic men-first evidence of the impact of an altered microenvironment.
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DOI:
10.1093/humrep/dey116
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发表时间:
2018-07-01
期刊:
Human reproduction (Oxford, England)
影响因子:
--
通讯作者:
Salonia A
Salonia A
中科院分区:
其他
文献类型:
--
作者:
Alfano M;Ferrarese R;Locatelli I;Ventimiglia E;Ippolito S;Gallina P;Cesana D;Canducci F;Pagliardini L;Viganò P;Clementi M;Nebuloni M;Montorsi F;Salonia A

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考虑到细胞外微环境在调节组织稳态中的相关作用,睾丸细菌微生物组(BM)是否与特发性非阻塞性无精子症(iNOA)的生殖细胞发育不全有关?在精子发生正常的睾丸中,与精子恢复阳性的iNOA和完全生殖细胞发育不全的iNOA相比,观察到生态失调的稳步增加。据报道,组织相关BM是许多身体栖息地的重要生物细胞外微环境成分,但尚未用于人类睾丸。横断面研究,调查了(i) 5名患有iNOA的男性在显微解剖睾丸精子提取(microTESE)中取回阴性精子的睾丸组织相关BM;(ii) 5名患有iNOA且在microTESE取精阳性的男性;(iii) 5名接受睾丸切除术的正常精子男性。对每个睾丸标本进行组织学分类,并根据细菌群落进行分析。应用大规模超深焦磷酸测序技术研究睾丸微生物组。宏基因组分析采用微生物生态学定量分析(QIIME)。通过数字液滴PCR定量组织相关细菌负荷。正常精子男性睾丸内有少量细菌,以放线菌门、拟杆菌门、厚壁菌门、变形菌门为主;iNOA个体的细菌DNA数量增加(P = 0.02),由于缺乏拟杆菌门和变形杆菌门而导致类群丰富度降低(P = 2 × 10−5)。精子回收阴性的标本显示生殖细胞发育不全,厚壁菌门和梭菌门进一步减少(P < 0.05),完全缺乏解糖胃杆菌,但放线菌门数量增加。在这个初步研究中分析的样本数量有限,值得外部验证。副肿瘤微环境可能对居住菌群产生影响。人类睾丸微环境并非微生物无菌,含有少量放线菌门、拟杆菌门、厚壁菌门和变形菌门。不良菌群与iNOA和完全生殖细胞发育不全有关。睾丸BM的新发现可以支持未来男性因素不育的转化治疗。本研究由泌尿外科研究所免费资助。作者声明没有利益冲突。N/A。
Given the relevant role of the extracellular microenvironment in regulating tissue homeostasis, is testicular bacterial microbiome (BM) associated with germ cell aplasia in idiopathic non-obstructive azoospermia (iNOA)? A steady increase of dysbiosis was observed among testis with normal spermatogenesis vs. iNOA with positive sperm retrieval and iNOA with complete germ cell aplasia. Tissue-associated BM has been reported to be a biologically important extracellular microenvironment component for numerous body habitats, but not yet for the human testis. Cross-sectional study, investigating tissue-associated BM in the testis of (i) five men with iNOA and negative sperm retrieval at microdissection testicular sperm extraction (microTESE); (ii) five men with iNOA and positive sperm retrieval at microTESE; and (iii) five normozoospermic men upon orchiectomy. Every testicular specimen was histologically classified and analyzed in terms of bacterial community. Massive ultra-deep pyrosequencing was applied to investigate testis microbiome. Metagenome was analyzed using Quantitative Insights Into Microbial Ecology (QIIME). Tissue-associated bacterial load was quantified by digital droplet PCR. Normozoospermic men showed small amounts of bacteria in the testis, with Actinobacteria, Bacteroidetes, Firmicutes Proteobacteria as the dominating phyla; iNOA individuals had increased amounts of bacterial DNA (P = 0.02), associated with decreased taxa richness due to the lack of Bacteroidetes and Proteobacteria (P = 2 × 10−5). Specimens with negative sperm retrieval at microTESE depicted complete germ cell aplasia and a further decrease in terms of Firmicutes and Clostridia (P < 0.05), a complete lack of Peptoniphilus asaccharolyticus, but increased amount of Actinobacteria. The limited number of specimens analyzed in this preliminary study deserves external validation. The paraneoplastic microenvironment could have an impact on the residential bacterial flora. Human testicular microenvironment is not microbiologically sterile, containing low amounts of Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria. A dysbiotic bacterial community was associated with iNOA and complete germ cell aplasia. Novel findings on testicular BM could support future translational therapies of male-factor infertility. This work was supported by URI-Urological Research Institute free funds. Authors declared no conflict of interest. N/A.
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