Yang Jia, Lu Zhaoxu, Liu Zhichao, Wang Li, Qiang Mei
Department of Children and Adolescences Health, School of Public Health, Shanxi Medical University, Taiyuan, China.
Front Genet. 2021 Jan 11;11:611276. doi: 10.3389/fgene.2020.611276. eCollection 2020.
Polycyclic aromatic hydrocarbons (PAHs) are known environmental pollutants. Studies are very limited regarding the impacts of paternal PAHs exposure on birth outcomes as well as the underpinning mechanisms in human. In this study, 302 reproductive-aged males (22-46 years old) were enrolled and demographic informatics data were obtained by questionnaires. The levels of urinary hydroxylated PAHs (OH-PAHs) were assessed by ultra-high performance liquid chromatography-tandem mass spectrometry; and methylation levels of the imprinting genes , , and of sperm DNA were evaluated via bisulfite pyrosequencing. The analysis of the correlation between OH-PAHs levels and methylation levels of imprinting genes showed that OH-PAHs are correlated with some CpG sites in , and . To further investigate an association of urinary OH-PAHs with birth outcomes, follow-up study of wives of these subjects has been performed for 1-3 years. As the result, a total of 157 babies were born. The birth outcomes parameters including birth weight (BW), length (BL), and ponderal index (PI) were recorded. The further analysis of generalized estimating equation indicated a negative correlation between urinary total OH-PAHs levels and newborn BW (β = -0.081, = 0.020); but this association has not been found for BL and PI. Furthermore, a logistic regression analysis was employed for examining associations of the methylation of imprinting genes with birth outcomes parameters, which indicated a negative correlation between BW and , namely, each unit percent (%) elevation in methylation of (but not and ) was significantly associated with a 0.135 g reduction of BW (β = -0.135; 95% CI 0.781-0.978). Putting together, these results show that paternal non-occupational environmental exposure to PAHs is associated with newborn BW. And imprinting gene methylation may be involved in the underlying mechanisms. This study in human population adds a support for previous animal study and implies that environmental impact on the offspring through paternal pathway.
多环芳烃（PAHs）是已知的环境污染物。关于父亲暴露于PAHs对出生结局的影响及其在人类中的潜在机制的研究非常有限。在本研究中，招募了302名生殖年龄男性（22 - 46岁），并通过问卷调查获取人口统计学数据。尿中羟基化多环芳烃（OH - PAHs）水平通过超高效液相色谱 - 串联质谱法评估；精子DNA印记基因、和的甲基化水平通过亚硫酸氢盐焦磷酸测序进行评估。OH - PAHs水平与印记基因甲基化水平的相关性分析表明，OH - PAHs与、和中的一些CpG位点相关。为了进一步研究尿中OH - PAHs与出生结局的关联，对这些受试者的妻子进行了1至3年的随访研究。结果，共出生157名婴儿。记录了包括出生体重（BW）、身长（BL）和 ponderal指数（PI）在内的出生结局参数。广义估计方程的进一步分析表明，尿中总OH - PAHs水平与新生儿BW呈负相关（β = - 0.081，= 0.020）；但未发现与BL和PI存在这种关联。此外，采用逻辑回归分析来检验印记基因甲基化与出生结局参数之间的关联，这表明BW与呈负相关，即（而非和）甲基化每升高一个单位百分比（%），BW显著降低0.135 g（β = - 0.135；95% CI 0.781 - 0.978）。综上所述，这些结果表明父亲非职业性环境暴露于PAHs与新生儿BW相关。印记基因甲基化可能参与其中的潜在机制。这项针对人类群体的研究为先前的动物研究提供了支持，并暗示环境通过父亲途径对后代产生影响。
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