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Article: Excessive ovarian stimulation up-regulates the Wnt-signaling molecule DKK1 in human endometrium and may affect implantation: An in vitro co-culture study

TitleExcessive ovarian stimulation up-regulates the Wnt-signaling molecule DKK1 in human endometrium and may affect implantation: An in vitro co-culture study
Authors
KeywordsEndometrium
Implantation
Ovarian stimulation
Spheroids
Wnt-signaling
Issue Date2010
PublisherOxford University Press. The Journal's web site is located at http://humrep.oxfordjournals.org/
Citation
Human Reproduction, 2010, v. 25 n. 2, p. 479-490 How to Cite?
AbstractBackground: High serum estradiol (E2) levels following ovarian stimulation lead to reduced implantation and pregnancy rates, yet the underlying mechanisms remain unknown. We investigated if aberrant expression of genes in the Wnt-signaling pathway may be involved. Methods: Microarray and real-time PCR analysis were performed to analyze gene expression profiles of endometrial samples taken at day hCG + 7 in stimulated cycles, and days LH + 7 and LH + 10 in natural cycles. Expression of several Wnt-signaling transcripts, including Dickkopf homolog 1 (DKK1), DKK2 and secreted frizzled-related protein 4 (sFRP4), was analyzed throughout the menstrual cycle. JAr spheroid/Ishikawa endometrial cell co-culture experiments were established to study effects of DKK1 on spheroid attachment in vitro. Results: We identified 351 differentially expressed genes. Endometrial samples taken at hCG + 7 had similar expression profiles to those at LH + 10. DKK1 transcripts were up-regulated and DKK2 and sFRP4 were down-regulated in the stimulated compared with LH + 7 group (all P < 0.05). DKK1 transcripts were low in proliferative phase (PS) and increased in late-secretory phase (LS, P < 0.05), although DKK2 peaked in mid-secretory phase (P < 0.05). sFRP4 transcripts were high in PS. Treatment of spheroid with recombinant human DKK-1 protein dose-dependently suppressed (P < 0.05 versus control) spheroids attachment onto endometrial cells (associated with decreased-catenin protein): this suppression was nullified by anti-DKK1 antibody.CONCLUSIONGene expression patterns in stimulated cycles resembled those of LS in natural cycles, when the implantation window is about to close, suggesting high serum E2 and/or progesterone concentrations may advance endometrial development, altering the implantation window and possibly decreasing pregnancy rate. Aberrant expression of DKK1 might impair embryo attachment and implantation in vivo.
Persistent Identifierhttp://hdl.handle.net/10722/135628
ISSN
2015 Impact Factor: 4.621
2015 SCImago Journal Rankings: 2.271
ISI Accession Number ID
Funding AgencyGrant Number
Committee on Research and Conference Grant
University of Hong Kong
Hong Kong Research Grant CouncilHKU7514/05M
Funding Information:

This work was supported in part by grants from the Committee on Research and Conference Grant, The University of Hong Kong to K. F. L. and Hong Kong Research Grant Council to P. C. H. (HKU7514/05M).

References

 

DC FieldValueLanguage
dc.contributor.authorLiu, Yen_HK
dc.contributor.authorKodithuwakku, SPen_HK
dc.contributor.authorNg, PYen_HK
dc.contributor.authorChai, Jen_HK
dc.contributor.authorNg, EHYen_HK
dc.contributor.authorYeung, WSBen_HK
dc.contributor.authorHo, PCen_HK
dc.contributor.authorLee, KFen_HK
dc.date.accessioned2011-07-27T01:37:58Z-
dc.date.available2011-07-27T01:37:58Z-
dc.date.issued2010en_HK
dc.identifier.citationHuman Reproduction, 2010, v. 25 n. 2, p. 479-490en_HK
dc.identifier.issn0268-1161en_HK
dc.identifier.urihttp://hdl.handle.net/10722/135628-
dc.description.abstractBackground: High serum estradiol (E2) levels following ovarian stimulation lead to reduced implantation and pregnancy rates, yet the underlying mechanisms remain unknown. We investigated if aberrant expression of genes in the Wnt-signaling pathway may be involved. Methods: Microarray and real-time PCR analysis were performed to analyze gene expression profiles of endometrial samples taken at day hCG + 7 in stimulated cycles, and days LH + 7 and LH + 10 in natural cycles. Expression of several Wnt-signaling transcripts, including Dickkopf homolog 1 (DKK1), DKK2 and secreted frizzled-related protein 4 (sFRP4), was analyzed throughout the menstrual cycle. JAr spheroid/Ishikawa endometrial cell co-culture experiments were established to study effects of DKK1 on spheroid attachment in vitro. Results: We identified 351 differentially expressed genes. Endometrial samples taken at hCG + 7 had similar expression profiles to those at LH + 10. DKK1 transcripts were up-regulated and DKK2 and sFRP4 were down-regulated in the stimulated compared with LH + 7 group (all P < 0.05). DKK1 transcripts were low in proliferative phase (PS) and increased in late-secretory phase (LS, P < 0.05), although DKK2 peaked in mid-secretory phase (P < 0.05). sFRP4 transcripts were high in PS. Treatment of spheroid with recombinant human DKK-1 protein dose-dependently suppressed (P < 0.05 versus control) spheroids attachment onto endometrial cells (associated with decreased-catenin protein): this suppression was nullified by anti-DKK1 antibody.CONCLUSIONGene expression patterns in stimulated cycles resembled those of LS in natural cycles, when the implantation window is about to close, suggesting high serum E2 and/or progesterone concentrations may advance endometrial development, altering the implantation window and possibly decreasing pregnancy rate. Aberrant expression of DKK1 might impair embryo attachment and implantation in vivo.en_HK
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://humrep.oxfordjournals.org/en_HK
dc.relation.ispartofHuman Reproductionen_HK
dc.rightsThis is a pre-copy-editing, author-produced PDF of an article accepted for publication in Human Reproduction following peer review. The definitive publisher-authenticated version Human Reproduction, 2010, v. 25 n. 2, p. 479-490 is available online at: http://humrep.oxfordjournals.org/content/25/2/479-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectEndometriumen_HK
dc.subjectImplantationen_HK
dc.subjectOvarian stimulationen_HK
dc.subjectSpheroidsen_HK
dc.subjectWnt-signalingen_HK
dc.subject.meshEmbryo Implantation - genetics-
dc.subject.meshEndometrium - drug effects - metabolism-
dc.subject.meshIntercellular Signaling Peptides and Proteins - biosynthesis-
dc.subject.meshOvulation Induction - adverse effects-
dc.subject.meshWnt Proteins - physiology-
dc.titleExcessive ovarian stimulation up-regulates the Wnt-signaling molecule DKK1 in human endometrium and may affect implantation: An in vitro co-culture studyen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0268-1161&volume=25&issue=2&spage=479&epage=490&date=2010&atitle=Excessive+ovarian+stimulation+up-regulates+the+Wnt-signaling+molecule+DKK1+in+human+endometrium+and+may+affect+implantation:+an+in+vitro+co-culture+study-
dc.identifier.emailChai, J:jchai@hkucc.hku.hken_HK
dc.identifier.emailNg, EHY:nghye@hkucc.hku.hken_HK
dc.identifier.emailYeung, WSB:wsbyeung@hkucc.hku.hken_HK
dc.identifier.emailHo, PC:pcho@hku.hken_HK
dc.identifier.emailLee, KF:ckflee@hku.hken_HK
dc.identifier.authorityChai, J=rp00241en_HK
dc.identifier.authorityNg, EHY=rp00426en_HK
dc.identifier.authorityYeung, WSB=rp00331en_HK
dc.identifier.authorityHo, PC=rp00325en_HK
dc.identifier.authorityLee, KF=rp00458en_HK
dc.description.naturepostprint-
dc.identifier.doi10.1093/humrep/dep429en_HK
dc.identifier.pmid19955106-
dc.identifier.scopuseid_2-s2.0-74549165387en_HK
dc.identifier.hkuros187010en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-74549165387&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume25en_HK
dc.identifier.issue2en_HK
dc.identifier.spage479en_HK
dc.identifier.epage490en_HK
dc.identifier.eissn1460-2350-
dc.identifier.isiWOS:000273703400027-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLiu, Y=23134878300en_HK
dc.identifier.scopusauthoridKodithuwakku, SP=8939085200en_HK
dc.identifier.scopusauthoridNg, PY=24174994900en_HK
dc.identifier.scopusauthoridChai, J=35200414100en_HK
dc.identifier.scopusauthoridNg, EHY=35238184300en_HK
dc.identifier.scopusauthoridYeung, WSB=7102370745en_HK
dc.identifier.scopusauthoridHo, PC=7402211440en_HK
dc.identifier.scopusauthoridLee, KF=26643097500en_HK

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