title: Triazole fungicide tebuconazole disrupts human placental trophoblast cell functions.
abstract: Triazole fungicides are one of the top ten classes of current-use pesticides. Although exposure to triazole fungicides is associated with reproductive toxicity in mammals, limited information is available regarding the effects of triazole fungicides on human placental trophoblast function. Tebuconazole (TEB) is a common triazole fungicide that has been extensively used for fungi control. In this work, we showed that TEB could reduce cell viability, disturb normal cell cycle distribution and induce apoptosis of human placental trophoblast cell line HTR-8/SVneo (HTR-8). Bcl-2 protein expression decreased and the level of Bax protein increased after TEB treatment in HTR-8 cells. The results demonstrated that this fungicide induced apoptosis of trophoblast cells via mitochondrial pathway. Importantly, we found that the invasive and migratory capacities of HTR-8 cells decreased significantly after TEB administration. TEB altered the expression of key regulatory genes involved in the modulation of trophoblast functions. Taken together, TEB suppressed human trophoblast invasion and migration through affecting the expression of protease, hormones, angiogenic factors, growth factors and cytokines. As the invasive and migratory abilities of trophoblast are essential for successful placentation and fetus development, our findings suggest a potential risk of triazole fungicides to human pregnancy.
authors: Key Laboratory of Environmental Remediation and Ecological Health, Ministry of Education, Zhejiang University, Hangzhou 310058, China.
authors: Jinghua
authors: J
authors: Zhou
authors: Research Center for Air Pollution and Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China.
authors: Jianyun
authors: J
authors: Zhang
authors: Zhejiang Key Laboratory of Organ Development and Regeneration, Institute of Developmental and Regenerative Biology, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 310036, China.
authors: Feixue
authors: F
authors: Li
authors: Key Laboratory of Environmental Remediation and Ecological Health, Ministry of Education, Zhejiang University, Hangzhou 310058, China; Research Center for Air Pollution and Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: jliue@zju.edu.cn.
authors: Jing
authors: J
authors: Liu
mesh_terms: D002460:Cell Line; D002468:Cell Physiological Phenomena / Q000187:drug effects*; D005260:Female; D005659:Fungicides, Industrial / Q000633:toxicity*; D006801:Humans; D010920:Placenta / Q000166:cytology; D011247:Pregnancy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014230:Triazoles / Q000633:toxicity*; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D005659:Fungicides, Industrial; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D014230:Triazoles; D051028:bcl-2-Associated X Protein; C087114:tebuconazole
keywords: Invasion; Tebuconazole; Toxicity; Triazole fungicides; Trophoblast