Dioxin-like rather than non-dioxin-like PCBs promote the development of endometriosis through stimulation of endocrine-inflammation interactions.
Polychlorinated biphenyls (PCBs) contain 209 congeners with various structure-activities. Exposure to PCBs was related to disorders of female reproduction. Endometriosis (EM) is an estrogen- and inflammation-dependent disease with high prevalence and severe health outcomes. Epidemiological studies have shown the effects of PCBs exposure on EM in regard to various structures of PCBs. However, little evidence is available from the toxicology considering the structure of PCBs. In the study, environmentally relevant concentrations of PCBs were used to treat primary cultured endometrial cells and an EM mouse model. Dioxin-like CB126, but not non-dioxin-like CB153, significantly enhanced 17β-estradiol (E2) biosynthesis in a dose-dependent manner. Among the genes related to estrogen metabolism, the level of 17β-hydroxysteroid dehydrogenase 7 (HSD17B7) showed significant increase following CB126 exposure. We further found that CB126 exposure decreased the methylation of the HSD17B7 promoter. Elevated expression of HSD17B7 was observed in the eutopic endometrium of EM patients. CB126 rather than CB153 triggered the inflammatory response by directly stimulating the secretion of inflammatory factors and indirectly reducing the level of lipoxin A4(LXA4). Furthermore, the inflammation enhanced the expression of HSD17B7. Antagonism of the aryl hydrocarbon receptor (AhR) diminished the effects induced by CB126. In vivo, the PCB-treated EM mouse model confirmed that CB126 rather than CB153 increased the levels of both E2 and inflammatory factors in peritoneal fluid and promoted the development of endometriotic lesions. In all, CB126, but not CB153, triggered EM development by stimulating estrogen biosynthesis, inflammation and their interactions and that these effects were mediated by the AhR receptor.
Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, People's Republic of China. qshuang@iue.ac.cn.
Qiansheng
Q
Huang
Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, People's Republic of China.
Yajie
Y
Chen
The First Affiliated Hospital of Xiamen University, Xiamen, 361003, People's Republic of China.
Qionghua
Q
Chen
Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, People's Republic of China.
Huanteng
H
Zhang
Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, People's Republic of China.
Yi
Y
Lin
The First Affiliated Hospital of Xiamen University, Xiamen, 361003, People's Republic of China.
Maobi
M
Zhu
Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, People's Republic of China. sjdong@iue.ac.cn.
Sijun
S
Dong
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D000072316:Dioxins and Dioxin-like Compounds / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004715:Endometriosis / Q000139:chemically induced* / Q000473:pathology; D004717:Endometrium / Q000166:cytology / Q000187:drug effects*; D004958:Estradiol / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism
D000072316:Dioxins and Dioxin-like Compounds; D018336:Receptors, Aryl Hydrocarbon; D004958:Estradiol; D011078:Polychlorinated Biphenyls; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase
Endometriosis; HSD17B7; LXA4; Methylation; Polychlorinated biphenyls