2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) suppresses spheroids attachment on endometrial epithelial cells through the down-regulation of the Wnt-signaling pathway

► TCDD suppresses β-catenin and E-cadherin expression in trophoblastic and endometrial cells. ► TCDD suppresses spheroids attachment onto endometrial cells. ► Activation of Wnt-signaling pathway via Wnt3a ligand or lithium chloride revert the suppressive effect of TCDD on β-catenin and E-cadherin ex...

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Bibliographic Details
Published in:Reproductive toxicology (Elmsford, N.Y.) N.Y.), 2012-01, Vol.33 (1), p.60-66
Main Authors: Tsang, Hilda, Cheung, Tsz-Yan, Kodithuwakku, Suranga P., Chai, Joyce, Yeung, William S.B., Wong, Chris K.C., Lee, Kai-Fai
Format: Article
Language:English
Subjects:
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Basic Helix-Loop-Helix Transcription Factors - drug effects
Basic Helix-Loop-Helix Transcription Factors - metabolism
beta Catenin - metabolism
Biological and medical sciences
Cadherins - metabolism
Canonical Wnt-signaling
Cell Adhesion - drug effects
Cell Line, Tumor
Coculture Techniques
Cytochrome P-450 CYP1A1 - biosynthesis
Dose-Response Relationship, Drug
Embryo Implantation - drug effects
Embryology: invertebrates and vertebrates. Teratology
Endometrium
Endometrium - drug effects
Endometrium - metabolism
Endometrium - pathology
Environmental Pollutants - toxicity
Enzyme Induction
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Epithelial Cells - pathology
Female
Fundamental and applied biological sciences. Psychology
Humans
Implantation
Medical sciences
Polychlorinated Dibenzodioxins - toxicity
Receptors, Aryl Hydrocarbon - drug effects
Receptors, Aryl Hydrocarbon - metabolism
Spheroids
Spheroids, Cellular
TCDD
Teratology. Teratogens
Toxicology
Trophoblasts - drug effects
Trophoblasts - metabolism
Trophoblasts - pathology
Wnt Signaling Pathway - drug effects
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Summary:► TCDD suppresses β-catenin and E-cadherin expression in trophoblastic and endometrial cells. ► TCDD suppresses spheroids attachment onto endometrial cells. ► Activation of Wnt-signaling pathway via Wnt3a ligand or lithium chloride revert the suppressive effect of TCDD on β-catenin and E-cadherin expression, and spheroid attachment. 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 10nM 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.
ISSN:0890-6238
1873-1708
DOI:10.1016/j.reprotox.2011.11.002