title: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) suppresses spheroids attachment on endometrial epithelial cells through the down-regulation of the Wnt-signaling pathway.
abstract: The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects embryo development, implantation and fertility in humans. The underlying molecular mechanism by which TCDD suppresses implantation remains largely unknown. We used the trophoblastic spheroids (embryo surrogate)-endometrial cells co-culture assay to study the attachment of trophoblastic spheroids (BeWo and Jeg-3) onto the endometrial epithelial (RL95-2 and Ishikawa) cells. TCDD dose-dependently induced cytochrome P450 1A1 (Cyp1A1) expression in trophoblastic and endometrial epithelial cells. Moreover, TCDD at 1 and 10 nM suppressed β-catenin (a Wnt-signaling molecule) and E-cadherin expression, as well as spheroids attachment onto endometrial cells. Interestingly, activation of the canonical Wnt-signaling pathway via Wnt3a or lithium chloride reverted the suppressive effect of TCDD on β-catenin and E-cadherin expressions in the BeWo and RL95-2 cells, and restored the spheroids attachment rate to be comparable to the untreated controls. Taken together, TCDD induces Cyp1A1 expression, modulates the Wnt-signaling pathway and suppresses spheroids attachment onto endometrial cells.
authors: Department of Obstetrics and Gynaecology, The University of Hong Kong, Hong Kong, China.
authors: Hilda
authors: H
authors: Tsang
authors: Tsz-Yan
authors: TY
authors: Cheung
authors: Suranga P
authors: SP
authors: Kodithuwakku
authors: Joyce
authors: J
authors: Chai
authors: William S B
authors: WS
authors: Yeung
authors: Chris K C
authors: CK
authors: Wong
authors: Kai-Fai
authors: KF
authors: Lee
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000187:drug effects / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D010064:Embryo Implantation / Q000187:drug effects*; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004785:Environmental Pollutants / Q000633:toxicity*; D004790:Enzyme Induction; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000378:metabolism; D018874:Spheroids, Cellular; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015820:Cadherins; D019363:Cytochrome P-450 CYP1A1; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D051176:beta Catenin; C111235:AHR protein, human; C495270:CTNNB1 protein, human