The Association of Certain Seminal Phthalate Metabolites on Spermatozoa Apoptosis: An Exploratory Mediation Analysis via Sperm Protamine
The Association of Certain Seminal Phthalate Metabolites on Spermatozoa Apoptosis: An Exploratory Mediation Analysis via Sperm Protamine
复制标题
某些精液邻苯二甲酸酯代谢物与精子凋亡的关联：通过精子鱼精蛋白进行的探索性中介分析
DOI：
10.1016/j.envpol.2022.118969
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发表时间：
2022
影响因子：
8.9
通讯作者：
Yang Pan
中科院分区：
文献类型：
--
作者：
Xiong Feng;Zhou Bin;Wu Nan-Xin;Deng Lang-Jing;Xie Jin-Ying;Li Xiao-Jie;Chen Ying-Jun;Wang Yi-Xin;Zeng Qiang;Yang Pan
早期的研究表明，暴露于邻苯二甲酸盐（PAEs）可能会诱导精子凋亡。精子精蛋白作为精子凋亡过程中的分子生物标志物可能介导PAE暴露与精子凋亡之间的关联。本研究旨在探讨精子精蛋白是否介导PAE暴露与精子凋亡的关联。我们测定了111名不育诊所男性的精子精蛋白水平、精浆中8种PAE代谢物浓度和3种精子凋亡参数。确定了PAEs作为单独的化学物质和与精蛋白的混合物的关联。通过中介分析探讨鱼精蛋白在PAEs与精子凋亡参数之间的中介作用。在调整混杂因素后，我们观察到精浆邻苯二甲酸单（2-乙基己基）酯（MEHP）浓度与精子精蛋白-1和精蛋白比例呈正相关。鱼精蛋白-1的MEHP浓度最高与最低四分位数的比较估计为4.65% (95% CI: 1.47%, 7.82%)，鱼精蛋白比的MEHP浓度为25.86% （95% CI: 3.05%, 53.73%）。分位数g计算模型显示，PAE混合物调整后的蛋白蛋白-1每四分位数增加9.42% (95% CI: 1.00, 20.92)， MEHP是主要贡献者。虽然PAE混合物与鱼精蛋白比例之间的联合关系可以忽略不计，但MEHP仍然被认为是主要的贡献者。此外，我们发现，相对于最低四分位数，Annexin V+/PI−精子中最高四分位数的鱼精蛋白-2和鱼精蛋白比值水平分别下降了43.45% （95% CI: 60.54%, - 19.75%）和122.55% （95% CI: 60.00%, 209.57%）。中介分析显示，鱼精蛋白比例显著介导了MEHP与膜联蛋白V+/PI−精子升高之间55.6%的相关性（5.13%;95% CI: 0.04%, 10.52%）。我们的研究结果提供了证据，表明人类暴露于PAEs与鱼精蛋白水平升高有关，鱼精蛋白水平升高可能介导精子凋亡过程。
Earlier studies have suggested that exposure to phthalates (PAEs) may induce spermatozoa apoptosis. Sperm protamine as a molecular biomarker during spermatozoa apoptotic processes may mediate the association between PAE exposure and spermatozoa apoptosis. This study aimed to explore whether sperm protamine mediates the association of PAE exposure with spermatozoa apoptosis. We determined sperm protamine levels, 8 PAE metabolite concentrations in seminal plasma, and 3 spermatozoa apoptosis parameters among 111 men from an infertility clinic. The associations of PAEs as individual chemicals and mixtures with sperm protamine were determined. The mediating roles of protamine in the associations between PAEs and spermatozoa apoptosis parameters were examined by mediation analysis. After adjusting for confounders, we observed positive correlations between seminal plasma concentrations of mono(2-ethylhexyl) phthalate (MEHP) and sperm protamine-1 and protamine ratio. Estimates comparing highest vs. lowest quartiles of MEHP concentration were 4.65% (95% CI: 1.47%, 7.82%) for protamine-1 and 25.86% (95% CI: 3.05%, 53.73%) for protamine ratio. The quantile g-computation models showed that the adjusted protamine-1 per quartile increase in PAE mixture was 9.42% (95% CI: 1.00, 20.92) with MEHP being the major contributor. Although the joint association between PAE mixture and protamine ratio was negligible, MEHP was still identified as the main contributor. Furthermore, we found that protamine-2 and protamine ratio levels in the highest quartiles exhibited a decrease of 43.45% (95% CI: 60.54%, −19.75%) and an increase of 122.55% (95% CI: 60.00%, 209.57%) in Annexin V+/PI−spermatozoa relative to the lowest quartiles, respectively. Mediation analysis revealed that protamine ratio significantly mediated 55.6% of the association between MEHP and Annexin V+/PI−spermatozoa elevation (5.13%; 95% CI: 0.04%, 10.52%). Our findings provided evidence that human exposure to PAEs was associated with increased protamine levels which may mediate the process of spermatozoa apoptosis.