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特发性不育患者的精液微生物群及其与精子DNA完整性的关系。

Seminal Microbiota of Idiopathic Infertile Patients and Its Relationship With Sperm DNA Integrity.

作者信息

Garcia-Segura Sergio, Del Rey Javier, Closa Laia, Garcia-Martínez Iris, Hobeich Carlos, Castel Ana Belén, Vidal Francisco, Benet Jordi, Ribas-Maynou Jordi, Oliver-Bonet Maria

机构信息

Unit of Cell Biology and Medical Genetics, Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona (UAB), Bellaterra, Spain.

Histocompatibility and Immunogenetics Laboratory, Banc de Sang i Teixits (BST), Barcelona, Spain.

出版信息

Front Cell Dev Biol. 2022 Jun 28;10:937157. doi: 10.3389/fcell.2022.937157. eCollection 2022.

Abstract

The development of new biomarkers for human male infertility is crucial to improve the diagnosis and the prognosis of this disease. Recently, seminal microbiota was shown to be related to sperm quality parameters, suggesting an effect in human fertility and postulating it as a biomarker candidate. However, its relationship to sperm DNA integrity has not been studied yet. The aim of the present study is to characterize the seminal microbiota of a western Mediterranean population and to evaluate its relationship to sperm chromatin integrity parameters, and oxidative stress. For that purpose, 14 samples from sperm donors and 42 samples from infertile idiopathic patients were obtained and were analyzed to assess the composition of the microbiota through full-length gene sequencing (Illumina MiSeq platform). Microbial diversity and relative abundances were compared to classic sperm quality parameters (macroscopic semen parameters, motility, morphology and concentration), chromatin integrity (global DNA damage, double-stranded DNA breaks and DNA protamination status) and oxidative stress levels (oxidation-reduction potential). The seminal microbiota observed of these samples belonged to the phyla , , and . The most abundant genera were , , , , , , , , , and . To our knowledge, this is the first detection of genus in seminal samples. Two clusters of microbial profiles were built based on a clustering analysis, and specific genera were found with different frequencies in relation to seminal quality defects. The abundances of several bacteria negatively correlate with the sperm global DNA fragmentation, most notably , and . The latter two were also associated with higher sperm motility and additionally with lower oxidative-reduction potential. , and correlated with reduced chromatin protamination status and increased double-stranded DNA fragmentation. These effects on DNA integrity coincide in many cases with the metabolism or enzymatic activities of these genera. Significant differences between fertile and infertile men were found in the relative presence of the family and the , and genera, which supports its possible involvement in male fertility. Our findings sustain the hypothesis that the seminal microbiome has an effect on male fertility.

摘要

开发用于诊断男性不育症的新型生物标志物对于改善该疾病的诊断和预后至关重要。最近,有研究表明精液微生物群与精子质量参数有关,这表明其对人类生育能力有影响,并假定它为生物标志物候选物。然而,其与精子DNA完整性的关系尚未得到研究。本研究的目的是对西地中海人群的精液微生物群进行特征分析,并评估其与精子染色质完整性参数和氧化应激的关系。为此,我们获取了14份来自精子捐献者的样本和42份来自特发性不育患者的样本,并通过全长基因测序(Illumina MiSeq平台)对这些样本进行分析,以评估微生物群的组成。将微生物多样性和相对丰度与经典的精子质量参数(宏观精液参数、活力、形态和浓度)、染色质完整性(总体DNA损伤、双链DNA断裂和DNA鱼精蛋白化状态)以及氧化应激水平(氧化还原电位)进行比较。观察到这些样本的精液微生物群属于 、 、 和 门。最丰富的属为 、 、 、 、 、 、 、 、 、 和 。据我们所知,这是首次在精液样本中检测到 属。基于聚类分析构建了两个微生物谱簇,发现特定属在精液质量缺陷方面的出现频率不同。几种细菌的丰度与精子总体DNA片段化呈负相关,最显著的是 、 和 。后两者还与较高的精子活力相关,此外还与较低的氧化还原电位相关。 、 和 与染色质鱼精蛋白化状态降低和双链DNA片段化增加相关。这些对DNA完整性的影响在许多情况下与这些属的代谢或酶活性一致。在可育和不育男性中, 科以及 、 和 属的相对存在存在显著差异,这支持了它们可能参与男性生育的观点。我们的研究结果支持精液微生物群对男性生育能力有影响这一假设。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e69/9275566/7676bec10eda/fcell-10-937157-g001.jpg

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