Zhu Wenwen, Fang Jiali, Ji Chenbo, Zhong Hong, Zhong Tianying, Cui Xianwei
Nanjing Women and Children's Healthcare Institute, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China.
Nanjing Women and Children's Healthcare Institute, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China.
Ecotoxicol Environ Saf. 2025 Jan 15;290:117596. doi: 10.1016/j.ecoenv.2024.117596. Epub 2024 Dec 21.
Neonicotinoids (NEOs) are well-designed highly selective pesticides that target nicotinic acetylcholine receptors. However, their extensive use, accumulation, and biomagnification pose significant risks to humans. Increasing evidence has suggested that NEOs may affect glucose homeostasis, but little research has linked NEOs exposure to gestational diabetes mellitus (GDM), which is the most common disease in pregnancy. We here aimed to investigate the association between NEOs exposure and GDM occurrence.
100 pregnant women who completed a 75 g oral glucose tolerance test (OGTT) at 24-28 weeks of gestation were enrolled. Urinary concentrations of seven widely used NEOs were quantified using ultra-high performance liquid chromatography multiple reaction monitoring mass spectrometry (UHPLC-MRM-MS/MS). Correlation analysis revealed the associations between NEOs concentrations and glucose homeostasis parameters. The toxic effects of thiamethoxam (TMX) and clothianidin (CLO) were assessed using pregnant mice, and the potential mechanism in impairing glucose disposition regarding brown adipose tissue (BAT) thermogenesis has been elucidated.
Among the 100 urine samples, 88 % were contaminated by NEOs with concentrations ranging from 2.50 to 491.34 nmol/L. TMX and CLO were the most frequently detected NEOs, highly detected in women with GDM. Moreover, we found statistically significant associations between TMX concentrations and 1hBG, and 2hBG. Exposure to mixed NEOs during gestation resulted in elevated glucose levels and impaired insulin sensitivity in normal pregnant and GDM mice models. In addition, we found the metabolic disorders induced by NEOs were linked to the deterioration of BAT thermogenesis in vivo.
In general, we demonstrated that prenatal exposures to NEOs were associated with an increased risk of GDM by deteriorating the thermogenic capacity of BAT.
新烟碱类农药（NEOs）是精心设计的高选择性杀虫剂，作用于烟碱型乙酰胆碱受体。然而，它们的广泛使用、积累和生物放大作用对人类构成了重大风险。越来越多的证据表明，新烟碱类农药可能会影响葡萄糖稳态，但很少有研究将新烟碱类农药暴露与妊娠期糖尿病（GDM）联系起来，而妊娠期糖尿病是孕期最常见的疾病。我们旨在研究新烟碱类农药暴露与妊娠期糖尿病发生之间的关联。
招募了100名在妊娠24 - 28周完成75克口服葡萄糖耐量试验（OGTT）的孕妇。使用超高效液相色谱多反应监测质谱法（UHPLC - MRM - MS/MS）对七种广泛使用的新烟碱类农药的尿液浓度进行定量。相关性分析揭示了新烟碱类农药浓度与葡萄糖稳态参数之间的关联。使用怀孕小鼠评估了噻虫嗪（TMX）和氯噻啉（CLO）的毒性作用，并阐明了其损害棕色脂肪组织（BAT）产热从而影响葡萄糖代谢的潜在机制。
在100份尿液样本中，88%被新烟碱类农药污染，浓度范围为2.50至491.34 nmol/L。TMX和CLO是最常检测到的新烟碱类农药，在妊娠期糖尿病女性中检测率很高。此外，我们发现TMX浓度与1小时血糖（1hBG）和2小时血糖（2hBG）之间存在统计学上的显著关联。在正常怀孕和妊娠期糖尿病小鼠模型中，孕期暴露于混合新烟碱类农药会导致血糖水平升高和胰岛素敏感性受损。此外，我们发现新烟碱类农药引起的代谢紊乱与体内棕色脂肪组织产热能力的下降有关。
总体而言，我们证明了产前暴露于新烟碱类农药会通过降低棕色脂肪组织的产热能力而增加患妊娠期糖尿病的风险。
