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尿邻苯二甲酸代谢物和脂质过氧化与精子线粒体 DNA 拷贝数和缺失的相关性研究。

Associations of urinary phthalate metabolites and lipid peroxidation with sperm mitochondrial DNA copy number and deletions.

机构信息

Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, 686 North Pleasant Street, Amherst, MA 01003, United States.

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Baystate Medical Center, 759 Chestnut Street, Springfield, MA 01199, United States.

出版信息

Environ Res. 2018 May;163:10-15. doi: 10.1016/j.envres.2018.01.023. Epub 2018 Feb 22.

Abstract

BACKGROUND

Phthalates, a chemical class of plasticizers, are ubiquitous environmental contaminants that have been associated with oxidative stress. Mitochondria DNA copy number (mtDNAcn) and DNA deletions (mtDNAdel) are emerging biomarkers for cellular oxidative stress and environment exposures.

OBJECTIVES

To examine associations of urinary phthalate metabolite and isoprostane concentrations on sperm mtDNAcn and mtDNAdel in male partners undergoing assisted reproductive technologies (ART).

METHODS

Ninety-nine sperm samples were collected from male partners undergoing ART at Baystate Medical Center in Springfield, MA as part of the Sperm Environmental Epigenetics and Development Study (SEEDS). Seventeen urinary phthalate metabolite concentrations were analyzed by the Centers for Disease Control using tandem mass spectrometry. Urinary 15-F2t-isoprostane concentrations, a biomarker of lipid peroxidation, were measured using a competitive enzyme-linked immunosorbent assay. A triplex qPCR method was used to determine the relative quantification of mtDNAcn and mtDNAdel.

RESULTS

Sperm mtDNAcn and mtDNAdel were positively correlated (Spearman rho = 0.31; p = .002). Adjusting for age, BMI, current smoking, race, and measurement batch, urinary monocarboxy-isononyl phthalate (MCNP) concentrations were positively associated with mtDNAcn (β = 1.63, 95% CI: 0.14, 3.11). Other urinary phthalate metabolite and isoprostane concentrations were not associated with sperm mtDNAcn or mtDNAdel.

CONCLUSIONS

Among this cohort of male ART participants, those with higher MCNP had higher mtDNAcn; other phthalate metabolites and isoprostane were not associated with mtDNAcn and mtDNAdel. Given our relatively small sample size, our results should be interpreted with caution. Future research is needed to replicate the findings in larger studies and among sperm samples obtained from the general population.

摘要

背景

邻苯二甲酸酯是一类化学增塑剂,广泛存在于环境中,与氧化应激有关。线粒体 DNA 拷贝数 (mtDNAcn) 和 DNA 缺失 (mtDNAdel) 是细胞氧化应激和环境暴露的新兴生物标志物。

目的

研究男性接受辅助生殖技术 (ART) 时,尿液中邻苯二甲酸代谢物和异前列腺素浓度与精子 mtDNAcn 和 mtDNAdel 的关系。

方法

在马萨诸塞州斯普林菲尔德的 Baystate 医疗中心,作为精子环境表观遗传学和发育研究 (SEEDS) 的一部分,从接受 ART 的男性伴侣中收集了 99 个精子样本。使用串联质谱法由疾病控制中心分析了 17 种尿液邻苯二甲酸代谢物浓度。使用竞争性酶联免疫吸附测定法测量尿液 15-F2t-异前列腺素浓度,这是脂质过氧化的生物标志物。使用三重 qPCR 方法确定 mtDNAcn 和 mtDNAdel 的相对定量。

结果

精子 mtDNAcn 和 mtDNAdel 呈正相关 (Spearman rho = 0.31;p =.002)。调整年龄、BMI、当前吸烟状况、种族和测量批次后,尿液中单羧酸异壬基邻苯二甲酸酯 (MCNP) 浓度与 mtDNAcn 呈正相关 (β = 1.63,95%CI:0.14,3.11)。其他尿液邻苯二甲酸代谢物和异前列腺素浓度与精子 mtDNAcn 或 mtDNAdel 无关。

结论

在本队列的男性 ART 参与者中,MCNP 较高的个体 mtDNAcn 较高;其他邻苯二甲酸代谢物和异前列腺素与 mtDNAcn 和 mtDNAdel 无关。鉴于我们的样本量相对较小,应谨慎解释我们的结果。需要进一步的研究在更大的研究中以及在一般人群中获得的精子样本中复制这些发现。

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