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精液中促炎细胞因子干扰素-γ(IFNG)和 C-X-C 基序趋化因子配体 8(CXCL8)在男性体内随时间波动。

Seminal plasma pro-inflammatory cytokines interferon-γ (IFNG) and C-X-C motif chemokine ligand 8 (CXCL8) fluctuate over time within men.

机构信息

Robinson Research Institute, Adelaide Medical School, University of Adelaide, Adelaide SA 5005, Australia.

School of Medicine, Flinders University, Adelaide SA 5001, Australia.

出版信息

Hum Reprod. 2017 Jul 1;32(7):1373-1381. doi: 10.1093/humrep/dex106.

Abstract

STUDY QUESTION

Do seminal plasma pro-inflammatory cytokines interferon-γ (IFNG) and C-X-C motif chemokine ligand 8 (CXCL8) vary within individual men over time?

SUMMARY ANSWER

IFNG exhibits substantial variation that is independent of duration of abstinence but correlates with lipopolysaccharide (LPS) content, while CXCL8 varies moderately in association with duration of abstinence.

WHAT IS KNOWN ALREADY

Pro-inflammatory cytokines IFNG and CXCL8 in seminal fluid can adversely impact male and female fertility. Other cytokines as well as sperm parameters fluctuate considerably within individuals over time, but whether IFNG and CXCL8 vary similarly, and the determinants of variance, are unknown.

STUDY DESIGN, SIZE, DURATION: Between two and seven semen samples were collected from 14 proven fertile donors at 6-10 week intervals over the course of ~12 months, to assess variation over time in cytokines and LPS, and to investigate relationships with sperm parameters and possible regulatory factors.

PARTICIPANTS/MATERIALS, SETTING, METHODS: The concentrations and total amounts per ejaculate of IFNG and CXCL8 were determined using commercial ELISA. Sperm parameters were assessed according to World Health Organization (WHO) IV standards and LPS was measured by limulus amebocyte lysate (LAL) assay. Mixed model analysis was utilized to determine the relative contribution of between- and within-individual factors in explaining variance. Relationships between cytokines, LPS and sperm parameters, as well as effect of age and duration of abstinence, were investigated by correlation analysis.

MAIN RESULTS AND THE ROLE OF CHANCE

Within-individual variability contributed to total variance particularly for both IFNG, CXCL8 and LPS, and was a stronger determinant than between-individual variability for IFNG and LPS. Normal sperm motility correlated inversely with CXCL8, and sperm concentration correlated inversely with LPS. Duration of abstinence was a determinant of total CXCL8, but not IFNG or LPS. Associations between LPS, IFNG and CXCL8 suggest IFNG and perhaps CXCL8 are influenced by microbial populations.

LIMITATIONS, REASONS FOR CAUTION: A limited number of donors from a single clinic were investigated. Clinical information on complete microbiology, BMI, nutrition, smoking and other lifestyle factors was unavailable. Further studies are required to determine whether the findings can be generalized to larger populations and different ethnicities.

WIDER IMPLICATIONS OF THE FINDINGS

These data reveal substantial variation over time in pro-inflammatory seminal fluid cytokines and imply existence of microbial or other environmental regulatory factors.

STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the National Health and Medical Research Council of Australia. The authors have no competing interests to disclose.

摘要

研究问题

个体男性的精液中促炎细胞因子干扰素-γ(IFNG)和 C-X-C 基序趋化因子配体 8(CXCL8)是否会随时间变化?

总结答案

IFNG 表现出大量的变化,与禁欲时间无关,但与脂多糖(LPS)含量相关,而 CXCL8 与禁欲时间相关,变化适度。

已知内容

精液中的促炎细胞因子 IFNG 和 CXCL8 可对男性和女性的生育能力产生不利影响。其他细胞因子以及精子参数在个体内部随时间波动很大,但 IFNG 和 CXCL8 是否会以类似的方式变化,以及变化的决定因素尚不清楚。

研究设计、大小、持续时间:在大约 12 个月的时间内,14 名已证明具有生育能力的供体每隔 6-10 周采集 2 到 7 份精液样本,以评估随时间推移细胞因子和 LPS 的变化,并研究与精子参数和可能的调节因素的关系。

参与者/材料、设置、方法:使用商业 ELISA 测定 IFNG 和 CXCL8 的浓度和每次射精的总量。精子参数根据世界卫生组织(WHO)IV 标准进行评估,LPS 通过鲎变形细胞溶解物(LAL)测定法测量。采用混合模型分析确定个体间和个体内因素在解释方差中的相对贡献。通过相关分析研究细胞因子、LPS 和精子参数之间的关系,以及年龄和禁欲时间的影响。

主要结果及其机遇作用

个体内的变异性对总方差的贡献特别大,无论是 IFNG、CXCL8 还是 LPS,并且对 IFNG 和 LPS 的个体间变异性的决定作用更强。正常精子活力与 CXCL8 呈负相关,精子浓度与 LPS 呈负相关。禁欲时间是总 CXCL8 的决定因素,但不是 IFNG 或 LPS。LPS、IFNG 和 CXCL8 之间的关联表明 IFNG 和可能的 CXCL8 受微生物群的影响。

局限性、谨慎的原因:仅从单个诊所调查了有限数量的供体。缺乏有关完整微生物群、BMI、营养、吸烟和其他生活方式因素的临床信息。需要进一步的研究来确定这些发现是否可以推广到更大的人群和不同的种族。

研究的意义

这些数据揭示了精液中促炎细胞因子随时间的显著变化,并暗示存在微生物或其他环境调节因素。

研究资金/利益冲突:本研究得到澳大利亚国家健康与医疗研究委员会的资助。作者没有利益冲突需要披露。

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