Urinary concentrations of phthalate and phthalate alternative metabolites and sperm DNA methylation: A multi-cohort and meta-analysis of men in preconception studies

Phthalates are ubiquitous pollutants in the environment; however, the mechanisms of phthalate-associated reproductive disorders in men are not fully understood. The aim of this study is to investigate associations between urinary phthalate metabolite concentrations and sperm DNA methylation. The study was conducted on 697 men from three prospective pregnancy cohorts: Longitudinal Investigation of Fertility and the Environment (LIFE) Study, Sperm Environmental Epigenetics and Development Study (SEEDS), and Environment and Reproductive Health (EARTH) Study. Eighteen phthalate and two phthalate alternative metabolites were quantified by mass spectrometry in preconception urinary samples and sperm DNA methylation was measured via Illumina EPIC Array (v1). Regional methylation analyses were conducted to identify cohort-specific loci associated with urinary phthalate metabolites.

邻苯二甲酸酯（phthalates）是环境中广泛存在的污染物，但目前尚未完全阐明邻苯二甲酸酯暴露与男性生殖功能异常的相关作用机制。本研究旨在探讨尿液中邻苯二甲酸酯代谢物浓度与精子DNA甲基化之间的关联。本研究共纳入来自3项前瞻性妊娠队列的697名男性受试者，分别为生育力与环境纵向调查（Longitudinal Investigation of Fertility and the Environment, LIFE）研究、精子环境表观遗传学与发育研究（Sperm Environmental Epigenetics and Development Study, SEEDS）以及环境与生殖健康（Environment and Reproductive Health, EARTH）研究。研究人员采用质谱法对孕前尿液样本中的18种邻苯二甲酸酯代谢物及2种邻苯二甲酸酯替代物代谢物进行定量检测，并通过Illumina EPIC芯片（v1）检测精子DNA甲基化水平。本研究开展区域甲基化分析，以识别与尿液邻苯二甲酸酯代谢物相关的队列特异性位点。