Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the immune system maternal-fetal interface during palatal development

Abstract

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an important environmental pollutant that disturbs the immune balance of the maternal-fetal interface (MFI) and is also a common environmental factor for the formation of cleft palate (CP). Therefore, the purpose is to investigate whether TCDD can cause CP by disrupting the immune balance of the maternal-fetal interface. Fifteen C57BL/6J mice were randomly assigned to three groups: control group, TCDD group, and TCDD plus Freund’s complete adjuvant (FCA) (TCDD + FCA) group. Peripheral blood, placentas, and palatal tissues were collected for H&E, flow cytometry, and ELISA. In the TCDD group, the placental diameter, the number of placental labyrinth vessels, and the area of sponge layer cells were all significantly reduced. At embryonic day (E) 17.0, there was a significant decrease in T-helper 1 (Th1) and Th2 cells in the peripheral blood of pregnant mice. Additionally, the levels of interferon-γ (IFN-γ) and interleukin-4 (IL-4), particularly IL-4, were significantly decreased. However, after treatment with FCA, the distance between the palatal shelves was reduced, and the placental weight, the number of labyrinth vessels, and the area of the cavernous cells in the placenta also increased. The number of Th1 and Th2 cells significantly increased, returning to the levels observed in the control group, with a more pronounced increase in the number of Th2 cells. In conclusion, TCDD may induce CP by disrupting the homeostasis of the MFI. The precise mechanisms by which TCDD impacts the immune system at the MFI require further investigation.2,3,7,8-四氯二苯并-对二恶英 （TCDD） 是一种重要的环境污染物，会扰乱母胎界面 （MFI） 的免疫平衡，也是形成腭裂 （CP） 的常见环境因素。因此，目的是研究 TCDD 是否可以通过破坏母胎界面的免疫平衡来引起 CP。将 15 只 C57BL/6J 小鼠随机分为 3 组：对照组、TCDD 组和 TCDD 加弗氏完全佐剂 （FCA） （TCDD + FCA） 组。收集外周血、胎盘和腭组织用于 H&E、流式细胞术和 ELISA。TCDD 组胎盘直径、胎盘迷路血管数量和海绵层细胞面积均显著减少。在胚胎第 17.0 天 （E） 时，妊娠小鼠外周血中的 T 辅助细胞 1 （Th1） 和 Th2 细胞显著减少。此外，干扰素-γ （IFN-γ） 和白细胞介素-4 （IL-4），特别是 IL-4 的水平显着降低。然而，用 FCA 处理后，腭架之间的距离减小，胎盘重量、迷路血管的数量和胎盘中海绵状细胞的面积也增加。Th1 和 Th2 细胞的数量显著增加，恢复到对照组观察到的水平，Th2 细胞的数量增加更明显。总之，TCDD 可能通过破坏 MFI 的稳态来诱导 CP。TCDD 影响 MFI 免疫系统的确切机制需要进一步研究。