在青春期（青春期前至性成熟）四个时间段内尿液中邻苯二甲酸代谢物浓度及其与俄罗斯年轻男性精液质量的关系。
Urinary phthalate metabolite concentrations during four windows spanning puberty (prepuberty through sexual maturity) and association with semen quality among young Russian men.
机构信息
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital & Harvard Medical School, Boston, USA; Departments of Environmental Health, Boston, USA.
Departments of Environmental Health, Boston, USA.
出版信息
Int J Hyg Environ Health. 2022 Jun;243:113977. doi: 10.1016/j.ijheh.2022.113977. Epub 2022 May 6.
AIM
To prospectively investigate the associations of urinary phthalate metabolite concentrations measured at four time points spanning pubertal development with semen parameters in Russian men.
DESIGN
516 boys were enrolled at ages 8-9 years (2003-2005) and followed annually.
METHODS
Urine samples were collected annually and pooled into four exposure windows [prepuberty, early puberty, late puberty and sexual maturity] based on physician assessed Tanner genitalia stages and testicular volume. Fifteen phthalate metabolites were quantified using isotope dilution HPLC-MS/MS at Moscow State University. We calculated molar sums (∑) of di-2-ethylhexyl phthalate (DEHP), di-isononyl phthalate (DiNP), di-isodecyl phthalate (DiDP) and anti-androgenic phthalate (AAP) metabolites. At sexual maturity (ages 18-19 years), the men provided 1-2 semen samples for analysis. We estimated the associations of quintiles of urinary ∑phthalate metabolites as well as mono-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), and mono-benzyl phthalate (MBzP) at each pubertal window, with semen parameters by fitting generalized linear mixed models with random intercepts and adjusting for confounders.
RESULTS
A total of 223 men who provided semen samples had phthalates measured at one or more pubertal windows. Higher urinary concentrations of ∑DiNP metabolites during late puberty were related to poorer semen quality (men with the highest quintile of urinary ∑DiNP had 30% lower sperm concentration, 32% lower count and 30% lower progressive motile count, compared to men in the lowest quintile). Also, young men with higher urinary concentrations of MiBP metabolites in early puberty tended to have poorer semen quality. No associations were observed for ∑DEHP metabolites, ∑DiDP metabolites, ∑AAP, MBzP or MnBP metabolites with semen quality parameters.
CONCLUSIONS
∑DiNP metabolites measured during late puberty and MiBP metabolites at early puberty were related to poorer semen quality, highlighting the importance of considering specific windows of exposure when investigating chemical exposures in relation to measures of reproductive health in men.
目的
前瞻性研究跨越青春期发育的四个时间点测量的尿邻苯二甲酸代谢物浓度与俄罗斯男性精液参数之间的关联。
设计
2003-2005 年，招募了 516 名 8-9 岁的男孩，并每年进行随访。
方法
每年采集尿液样本，并根据医生评估的生殖器和睾丸体积分期，将尿液样本分为四个暴露窗[青春期前、早期青春期、晚期青春期和性成熟期]进行混合。使用同位素稀释高效液相色谱-串联质谱法（HPLC-MS/MS）对 15 种邻苯二甲酸代谢物进行定量。我们计算了二-2-乙基己基邻苯二甲酸酯（DEHP）、二异壬基邻苯二甲酸酯（DiNP）、二异癸基邻苯二甲酸酯（DiDP）和抗雄激素性邻苯二甲酸酯（AAP）代谢物的摩尔总和（∑）。在性成熟期（18-19 岁），男性提供 1-2 份精液样本进行分析。我们通过拟合具有随机截距的广义线性混合模型，并调整混杂因素，估计了每个青春期窗口的尿液∑邻苯二甲酸代谢物以及单丁基邻苯二甲酸酯（MnBP）、单异丁基邻苯二甲酸酯（MiBP）和单苄基邻苯二甲酸酯（MBzP）的五分位数与精液参数的关联。
结果
共有 223 名提供精液样本的男性在一个或多个青春期窗口测量了邻苯二甲酸盐。青春期后期尿液中∑DiNP 代谢物浓度较高与精液质量较差有关（与最低五分位数的男性相比，尿液中∑DiNP 代谢物浓度最高的男性精子浓度降低 30%，计数降低 32%，前向运动精子计数降低 30%）。此外，青春期早期尿液中 MiBP 代谢物浓度较高的年轻男性精液质量也较差。∑DEHP 代谢物、∑DiDP 代谢物、∑AAP、MBzP 或 MnBP 代谢物与精液质量参数之间没有关联。
结论
青春期后期测量的∑DiNP 代谢物和青春期早期的 MiBP 代谢物与精液质量较差有关，这突出表明在研究与男性生殖健康相关的化学暴露时，考虑特定的暴露窗口期的重要性。
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