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Article: The fungicide Mancozeb reduces spheroid attachment onto endometrial epithelial cells through downregulation of estrogen receptor β and integrin β3 in Ishikawa cells

TitleThe fungicide Mancozeb reduces spheroid attachment onto endometrial epithelial cells through downregulation of estrogen receptor β and integrin β3 in Ishikawa cells
Authors
KeywordsMancozeb
ETU
Spheroid attachment
Microarray
Endometrial receptivity
Steroid hormone receptors
Issue Date2021
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ecoenv
Citation
Ecotoxicology and Environmental Safety, 2021, v. 208, article no. 111606 How to Cite?
AbstractMancozeb is a metal-containing ethylene bis-dithiocarbamate fungicide widely used in agriculture. Ethylene thiourea (ETU) is the primary metabolite of Mancozeb. Mancozeb has been associated with spontaneous abortions and abnormal menstruation in women. However, the effects of Mancozeb and ETU on embryo attachment remain unknown. The human blastocyst surrogate trophoblastic spheroids (JEG-3), endometrial epithelial surrogate adenocarcinoma cells (Ishikawa), or human primary endometrial epithelial cells (EECs) monolayer were used in the spheroid attachment models. Ishikawa and EECs were pretreated with different concentrations of Mancozeb or ETU for 48 h before the attachment assay. Gene expression profiles of Ishikawa cells were examined to understand how Mancozeb modulates endometrial receptivity with Microarray. The genes altered by Mancozeb were confirmed by qPCR and compared with the ETU treated groups. Mancozeb and ETU treatment inhibited cell viability at 10 μg/mL and 5000 µg/mL, respectively. At non-cytotoxic concentrations, Mancozeb at 3 μg/mL and ETU at 300 μg/mL reduced JEG-3 spheroid attachment onto Ishikawa cells. A similar result was observed with human primary endometrial epithelial cells. Mancozeb at 3 μg/mL modified the transcription of 158 genes by at least 1.5-fold in Microarray analysis. The expression of 10 differentially expressed genes were confirmed by qPCR. Furthermore, Mancozeb decreased spheroid attachment possibly through downregulating the expression of endometrial estrogen receptor β and integrin β3, but not mucin 1. These results were confirmed in both overexpression and knockdown experiments and co-culture assay. Mancozeb but not its metabolite ETU reduced spheroid attachment through modulating gene expression profile and decreasing estrogen receptor β and integrin β3 expression of endometrial epithelial cells.
Persistent Identifierhttp://hdl.handle.net/10722/307959
ISSN
2023 Impact Factor: 6.2
2023 SCImago Journal Rankings: 1.418
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, Z-
dc.contributor.authorKottawatta, KSA-
dc.contributor.authorKodithuwakku, SP-
dc.contributor.authorFernando, TS-
dc.contributor.authorLee, YL-
dc.contributor.authorNg, EHY-
dc.contributor.authorYeung, WSB-
dc.contributor.authorLee, KF-
dc.date.accessioned2021-11-12T13:40:24Z-
dc.date.available2021-11-12T13:40:24Z-
dc.date.issued2021-
dc.identifier.citationEcotoxicology and Environmental Safety, 2021, v. 208, article no. 111606-
dc.identifier.issn0147-6513-
dc.identifier.urihttp://hdl.handle.net/10722/307959-
dc.description.abstractMancozeb is a metal-containing ethylene bis-dithiocarbamate fungicide widely used in agriculture. Ethylene thiourea (ETU) is the primary metabolite of Mancozeb. Mancozeb has been associated with spontaneous abortions and abnormal menstruation in women. However, the effects of Mancozeb and ETU on embryo attachment remain unknown. The human blastocyst surrogate trophoblastic spheroids (JEG-3), endometrial epithelial surrogate adenocarcinoma cells (Ishikawa), or human primary endometrial epithelial cells (EECs) monolayer were used in the spheroid attachment models. Ishikawa and EECs were pretreated with different concentrations of Mancozeb or ETU for 48 h before the attachment assay. Gene expression profiles of Ishikawa cells were examined to understand how Mancozeb modulates endometrial receptivity with Microarray. The genes altered by Mancozeb were confirmed by qPCR and compared with the ETU treated groups. Mancozeb and ETU treatment inhibited cell viability at 10 μg/mL and 5000 µg/mL, respectively. At non-cytotoxic concentrations, Mancozeb at 3 μg/mL and ETU at 300 μg/mL reduced JEG-3 spheroid attachment onto Ishikawa cells. A similar result was observed with human primary endometrial epithelial cells. Mancozeb at 3 μg/mL modified the transcription of 158 genes by at least 1.5-fold in Microarray analysis. The expression of 10 differentially expressed genes were confirmed by qPCR. Furthermore, Mancozeb decreased spheroid attachment possibly through downregulating the expression of endometrial estrogen receptor β and integrin β3, but not mucin 1. These results were confirmed in both overexpression and knockdown experiments and co-culture assay. Mancozeb but not its metabolite ETU reduced spheroid attachment through modulating gene expression profile and decreasing estrogen receptor β and integrin β3 expression of endometrial epithelial cells.-
dc.languageeng-
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ecoenv-
dc.relation.ispartofEcotoxicology and Environmental Safety-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectMancozeb-
dc.subjectETU-
dc.subjectSpheroid attachment-
dc.subjectMicroarray-
dc.subjectEndometrial receptivity-
dc.subjectSteroid hormone receptors-
dc.titleThe fungicide Mancozeb reduces spheroid attachment onto endometrial epithelial cells through downregulation of estrogen receptor β and integrin β3 in Ishikawa cells-
dc.typeArticle-
dc.identifier.emailLee, YL: cherielee@hku.hk-
dc.identifier.emailNg, EHY: nghye@hku.hk-
dc.identifier.emailYeung, WSB: wsbyeung@hku.hk-
dc.identifier.emailLee, KF: ckflee@hku.hk-
dc.identifier.authorityLee, YL=rp00308-
dc.identifier.authorityNg, EHY=rp00426-
dc.identifier.authorityYeung, WSB=rp00331-
dc.identifier.authorityLee, KF=rp00458-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.ecoenv.2020.111606-
dc.identifier.pmid33396126-
dc.identifier.scopuseid_2-s2.0-85095983338-
dc.identifier.hkuros329640-
dc.identifier.volume208-
dc.identifier.spagearticle no. 111606-
dc.identifier.epagearticle no. 111606-
dc.identifier.isiWOS:000604142700001-
dc.publisher.placeUnited States-

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