Wen Juan, Geng Shijie, Mu Juan, Wang Junya, Dai Yongmei, Hu Lingmin
Nanjing Women and Children's Healthcare Institute, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, Jiangsu, 210004, PR China; Department of Nutrition, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, Jiangsu, 210004, PR China.
Nanjing Women and Children's Healthcare Institute, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, Jiangsu, 210004, PR China.
Environ Pollut. 2025 May 1;372:126069. doi: 10.1016/j.envpol.2025.126069. Epub 2025 Mar 14.
Pentachlorophenol (PCP) is a pervasive endocrine-disrupting compound present in the environment. Limited research has explored the effects of PCP exposure on gestational diabetes mellitus (GDM), particularly the metabolites-related mechanism. Our study seeks to characterize the interrelationships between PCP exposure, plasma metabolomic markers, and GDM, aiming to elucidate the metabolomic profile mediating PCP-GDM relationship. From a prospective cohort in Changzhou, China, a nested case-control study was conducted, involving 154 GDM cases and 308 controls. We collected fasting blood samples before 16 weeks of gestation and determined PCP levels by UPLC-MS/MS. Plasma metabolomic markers were identified using untargeted metabolomics. Multivariate logistic regression and mediation analysis were used to examine the relationships among PCP exposure, metabolomic markers, and GDM. Using the Mann-Whitney U test, we found that serum PCP levels were significantly higher in GDM cases (median: 0.43 ng/mL, IQR: 0.28-0.77) compared to controls (median: 0.38 ng/mL, IQR: 0.24-0.64; P = 0.041). In the fully adjusted model, which additionally accounted for dietary patterns, the OR (95 %CI) values for GDM across tertiles of serum PCP were 1 (reference), 1.24 (0.73, 2.11), and 2.17 (1.28, 3.68), respectively, indicating a potential dose-response relationship (P trend = 0.004). Furthermore, 152 differential metabolites were identified between groups (FDR <0.05), implicating 4 metabolic pathways: "Nitrogen metabolism", "Alanine, aspartate and glutamate metabolism", "Glycerophospholipid metabolism", and "Pyrimidine metabolism" (FDR <0.1). Mediation analysis revealed that 5 metabolomic markers (such as N-Acetylalanine and 4-Acetamidobutyric acid) significantly mediated the association between PCP and GDM (FDR <0.05), with mediated proportions ranging from 0.15 to 0.31. Together, pregnant women in Eastern China exhibit widespread PCP exposure, with serum PCP levels positively associated with GDM risk. PCP exposure-related metabolomic changes may partially mediate the link between PCP and GDM.
五氯苯酚（PCP）是一种普遍存在于环境中的内分泌干扰化合物。关于PCP暴露对妊娠期糖尿病（GDM）影响的研究有限，尤其是与代谢物相关的机制。我们的研究旨在描述PCP暴露、血浆代谢组学标志物与GDM之间的相互关系，以阐明介导PCP与GDM关系的代谢组学特征。在中国常州的一个前瞻性队列中进行了一项巢式病例对照研究，包括154例GDM病例和308例对照。我们在妊娠16周前采集空腹血样，通过超高效液相色谱-串联质谱法（UPLC-MS/MS）测定PCP水平。使用非靶向代谢组学鉴定血浆代谢组学标志物。采用多变量逻辑回归和中介分析来研究PCP暴露、代谢组学标志物与GDM之间的关系。通过曼-惠特尼U检验，我们发现GDM病例的血清PCP水平（中位数：0.43 ng/mL，四分位间距：0.28 - 0.77）显著高于对照组（中位数：0.38 ng/mL，四分位间距：0.24 - 0.64；P = 0.041）。在进一步考虑饮食模式的完全调整模型中，血清PCP三分位数分组中GDM的比值比（95%置信区间）值分别为1（参考值）、1.24（0.73，2.11）和2.17（1.28，3.68），表明存在潜在的剂量反应关系（P趋势 = 0.004）。此外，两组之间鉴定出152种差异代谢物（假发现率<0.05），涉及4条代谢途径：“氮代谢”、“丙氨酸、天冬氨酸和谷氨酸代谢”、“甘油磷脂代谢”和“嘧啶代谢”（假发现率<0.1）。中介分析显示，5种代谢组学标志物（如N - 乙酰丙氨酸和4 - 乙酰氨基丁酸）显著介导了PCP与GDM之间的关联（假发现率<0.05），介导比例范围为0.15至0.31。总之，中国东部的孕妇普遍存在PCP暴露，血清PCP水平与GDM风险呈正相关。PCP暴露相关的代谢组学变化可能部分介导了PCP与GDM之间的联系。
