title: Disruption of the hormonal network and the enantioselectivity of bifenthrin in trophoblast: maternal-fetal health risk of chiral pesticides.
abstract: Endocrine-disrupting chemicals (EDCs) can interfere with normal hormone signaling to increase health risks to the maternal-fetal system, yet few studies have been conducted on the currently used chiral EDCs. This work tested the hypothesis that pyrethroids could enantioselectively interfere with trophoblast cells. Cell viability, hormone secretion, and steroidogenesis gene expression of a widely used pyrethroid, bifenthrin (BF), were evaluated in vitro, and the interactions of BF enantiomers with estrogen receptor (ER) were predicted. At low or noncytotoxic concentrations, both progesterone and human chorionic gonadotropin secretion were induced. The expression levels of progesterone receptor and human leukocyte antigen G genes were significantly stimulated. The key regulators of the hormonal cascade, GnRH type-I and its receptor, were both upregulated. The expression levels of selected steroidogenic genes were also significantly altered. Moreover, a consistent enantioselective interference of hormone signaling was observed, and S-BF had greater effects than R-BF. Using molecular docking, the enantioselective endocrine disruption of BF was predicted to be partially due to enantiospecific ER binding affinity. Thus, BF could act through ER to enantioselectively disturb the hormonal network in trophoblast cells. These converging results suggest that the currently used chiral pesticides are of significant concern with respect to maternal-fetal health.
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology , Hangzhou 310032, China.
authors.forename: Meirong
authors.initials: M
authors.lastname: Zhao
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shulin
authors.initials: S
authors.lastname: Zhuang
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Chengsheng
authors.initials: C
authors.lastname: Lu
authors.forename: Weiping
authors.initials: W
authors.lastname: Liu
mesh_terms: D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D052244:Endocrine Disruptors / Q000737:chemistry / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D059951:HLA-G Antigens / Q000235:genetics / Q000378:metabolism; D006262:Health; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D010575:Pesticides / Q000737:chemistry / Q000633:toxicity*; D017434:Protein Structure, Tertiary; D011722:Pyrethrins / Q000737:chemistry / Q000633:toxicity*; D011960:Receptors, Estrogen / Q000737:chemistry / Q000378:metabolism; D011966:Receptors, LHRH / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012307:Risk Factors; D013237:Stereoisomerism; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D052244:Endocrine Disruptors; D059951:HLA-G Antigens; D006728:Hormones; D010575:Pesticides; D011722:Pyrethrins; D011960:Receptors, Estrogen; D011966:Receptors, LHRH; D011980:Receptors, Progesterone; D007987:Gonadotropin-Releasing Hormone; C099952:bifenthrin