Wang Cui, Yang Jinhuan, Hao Zhengliang, Gong Chenxue, Tang Lihua, Xu Yingling, Lu Dezhao, Li Zhuoyu, Zhao Meirong
College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Environ Pollut. 2017 Dec;231(Pt 1):1172-1180. doi: 10.1016/j.envpol.2017.08.029. Epub 2017 Sep 19.
Epidemiological studies have exhibited a positive association between fine particulate matter (PM) exposure and adverse pregnancy outcome (APO). However, source-related effect and the potential mechanism have not been thoroughly elucidated in toxicology. In this study, PM was collected during a severe winter haze episode in an energy-base city of China. We coupled this approach with the source appointment by applying the Lagrangian Integrated Trajectory and Concentration Weighted Trajectory model. We observed that the primary trajectory with high polluted air mass came from the northwest of the sampling site. Approximately 90% or more of PM was derived from the industry at this haze period. Next, the sampled PM was used to study the classical hormone synthesis pathway on trophoblast JEG-3 cells. PM induced the secretion of human chorionic gonadotrophin (HCG) and the proliferation of JEG-3 cells at a noncytotoxic concentration. However, the synthesis of progesterone was significantly suppressed, even if both hCG and cyclic adenosine monophosphate (cAMP) were increased, suggesting that PM may interfere the downstream of cAMP. As expected, the phosphorylated activity of protein kinase A (PKA) was attenuated. Subsequently, the downstream molecules of steroidogenesis, such as ferredoxin reductase (FDXR), CYP11A1 (encoded P450scc), and 3β-Hydroxysteroid dehydrogenase type 1 (3β-HSD1), were inhibited. Therefore, PM primarily derived from industry, may directly inhibit the phosphorylation status of PKA in JEG-3 which, in turn, inhibited the proteins expression in progesterone-synthesis to suppress progesterone levels. Considering the pivotal role of progesterone in pregnancy maintenance, the mechanism on hormone synthesis may provide a better understanding for PM-caused APO. Industry-emanated PM, though not specific, could threaten the placenta, which needs to be verified by further epidemiological studies.
流行病学研究表明，暴露于细颗粒物（PM）与不良妊娠结局（APO）之间存在正相关。然而，毒理学中与来源相关的影响和潜在机制尚未得到充分阐明。在本研究中，在中国一个以能源为基础的城市严重冬季雾霾事件期间收集了PM。我们通过应用拉格朗日综合轨迹和浓度加权轨迹模型，将这种方法与源定位相结合。我们观察到，高污染气团的主要轨迹来自采样点的西北部。在这个雾霾期间，约90%或更多的PM来自工业。接下来，将采样的PM用于研究滋养层JEG-3细胞上的经典激素合成途径。在非细胞毒性浓度下，PM诱导了人绒毛膜促性腺激素（HCG）的分泌和JEG-3细胞的增殖。然而，即使hCG和环磷酸腺苷（cAMP）都增加，孕酮的合成也被显著抑制，这表明PM可能干扰了cAMP的下游。正如预期的那样，蛋白激酶A（PKA）的磷酸化活性减弱。随后，类固醇生成的下游分子，如铁氧化还原蛋白还原酶（FDXR）、CYP11A1（编码P450scc）和1型3β-羟基类固醇脱氢酶（3β-HSD1），受到抑制。因此，主要来源于工业的PM可能直接抑制JEG-3中PKA的磷酸化状态，进而抑制孕酮合成中的蛋白质表达，以抑制孕酮水平。考虑到孕酮在维持妊娠中的关键作用，激素合成机制可能为PM导致的APO提供更好的理解。工业排放的PM虽然不具有特异性，但可能威胁胎盘，这需要进一步的流行病学研究来验证。
