SO2 derivatives induce dysfunction in human trophoblasts via inhibiting ROS/IL-6/STAT3 pathway

Ecotoxicology and Environmental Safety

Hailie Chen¹  Bingqian Huang¹  Jianping Tan¹  Liqiong Zhu²  Lihao Hu²  Shiyu Bai²  Yong Liu²  Yukun Liu²  Hui Chen³  Jianping Zhang³ 

[1] Center for Reproductive Genetics and Reproductive Medicine, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China;Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China;Hematologic Lab of Pediatrics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China;

关键词: Sulfur dioxides;    Placental trophoblast;    ROS;    Interleukin-6;    STAT3;    Cellular dysfunction;   

DOI  :  

来源: DOAJ

【 摘 要 】

Background: Epidemiological studies have revealed that sulfur dioxides (SO2) can increase the risk of pregnancy complications such as missed abortion in the first trimester, stillbirth, preterm birth, small for gestational age, gestational diabetes mellitus and preeclampsia, but the mechanisms underlying these findings remains unknown. What is known, however, is that trophoblasts, a type of fetal cell exerting vital immunologic functions to maintain a successful pregnancy, are usually involved in the pathogenic mechanism of pregnancy complications. Objective: To study the effect of SO2 derivatives (bisulfite and sulfite, 1:3 M/M) on the function of trophoblasts. Methods: Swan.71 trophoblast cells were treated with various concentrations of SO2 derivatives to determine the effect of SO2 derivatives on cellular viability by CKK8. Flow cytometry was performed to analyze the effect of SO2 derivatives on apoptosis, cell cycle and intracellular ROS. Wound healing assay and transwell assay were conducted to examine the migration and invasion of Swan.71 cells. Inflammation-related cytokines in the supernatant (IL-1β, IL-6, IL-8, IL-10 and TNF-α) were measured by IMMULITE®1000 Systems (SIEMENS). The expression level of NLRP3, Caspase1, MMP9, MMP2, STAT3, and p-STAT3 were evaluated by Western Blotting. Results: Exposure to SO2 derivatives significantly decreased cellular viability, arrested cell cycle at S/G2/M phase and induced cell apoptosis of Swan.71 trophoblasts. In addition, the migration and invasion of Swan.71 cell were significantly inhibited. SO2 derivatives also significantly increased IL-1β secretion while it is NLRP3/Caspase1 independent. IL-6 secretion was significant inhibited accompanied by decreased STAT3 phosphorylation and expression of MMP2 and MMP9. The intracellular ROS level was significantly suppressed by SO2 derivatives. Conclusion: SO2 derivatives exert toxic effects on trophoblasts which results in: suppressing cellular viability and intracellular ROS level, interfering with cell proliferation through arresting cell cycle, inducing cell apoptosis, disturbing inflammation-related cytokines secretion and inhibiting motility. Decreased ROS/IL-6/STAT3 levels play a role in inhibited cell viability, cell cycle arrest, apoptosis and defective motility.

【 授权许可】

Unknown