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Article: MicroRNA Let-7a and dicer are important in the activation and implantation of delayed implanting mouse embryos

TitleMicroRNA Let-7a and dicer are important in the activation and implantation of delayed implanting mouse embryos
Authors
KeywordsDicer
Dormant blastocyst
Embryo implantation
Estradiol activation
MicroRNA
Issue Date2014
PublisherOxford University Press. The Journal's web site is located at http://humrep.oxfordjournals.org/
Citation
Human Reproduction, 2014, v. 29 n. 4, p. 750-762 How to Cite?
Abstractstudy question:Does Let-7a have a functional role in modulating dicer expression to activate dormant mouse blastocysts for implantation? summaryanswer:Let-7a post-transcriptionally regulates dicer expression altering microRNA expression to affect the implantation competency of the activated blastocysts. what is known already:The Let-7a microRNA is up-regulated during blastocyst dormancy and its forced-expression suppresses embryo implantationin vitro andin vivo. Dicer is a Let-7 target, which processes pre-microRNA to mature microRNA. study design, size, duration:The effects on the expression of Let-7a and dicer in dormant blastocysts during the first 12 h after estradiol-induced activation, and the relationship between Let-7a and dicer in preimplantation embryos were determined. The effects on the microRNAexpression and embryo implantationin vivoin dicer-knockdown mouse 5 –8 cell embryos and dormant blastocysts at 1 h post estradiol activation were also studied. participants/materials, setting, methods:ICR female mice at 6 weeks of age were ovariectomized on Day 4 of pregnancy to generate the delayed implantation model. Mouse 5–8 cell embryos and/or dormant blastocysts at 1 h after estradiol injection were electroporated with dicer siRNA and Let-7a precursor or Let-7a inhibitor. At 48 h post electroporation, the Let-7a expression, dicer transcripts and proteins in the embryos were determined using qPCR and immunostaining/western blotting, respectively. All experiments were repeated at least three times. main results and the role of chance:Estradiol injection down-regulated Let-7a and up-regulated dicer in the dormant blastocysts during the first 12 h post-activation. Dicer knockdown at 1 h post-activation of blastocysts suppressed EGFR expression, attenuated EGF binding and compromised implantation of the transferred embryos. Let-7a transcriptionally regulated dicer by binding to the 3 ′ -UTR of dicer in trophoblast cells. Dicer knockdown in blastocysts suppressed mature Let-7a expression and compromised implantation. limitations, reasons for caution:Gain- and loss-of-function approaches were used by analyzing transient expressions of transfected microRNA modulators or genes. The consequence of the Let-7a-dicer interaction on pregnancy remains to be determined. The study used the mouse as a model and the applicability of the observed phenomena in humans warrants further investigation. wider implications of the findings:Our results indicate that the Let-7a-dicer interaction leads to differential microRNA expression in dormant blastocysts after estradiol activation. Because the expression pattern of Let-7a in human blastocysts is similar to that in mouse blastocysts, our observation that the Let-7a-dicer interaction has a role in regulating the implantation potential of the mouse blastocysts could be applicable to humans.
Persistent Identifierhttp://hdl.handle.net/10722/196810
ISSN
2020 Impact Factor: 6.918
2020 SCImago Journal Rankings: 2.446
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCheong, WYAen_US
dc.contributor.authorPang, RTKen_US
dc.contributor.authorLiu, Wen_US
dc.contributor.authorKottawatta, KSAen_US
dc.contributor.authorLee, CKFen_US
dc.contributor.authorYeung, WSBen_US
dc.date.accessioned2014-04-29T03:42:52Z-
dc.date.available2014-04-29T03:42:52Z-
dc.date.issued2014en_US
dc.identifier.citationHuman Reproduction, 2014, v. 29 n. 4, p. 750-762en_US
dc.identifier.issn0268-1161-
dc.identifier.urihttp://hdl.handle.net/10722/196810-
dc.description.abstractstudy question:Does Let-7a have a functional role in modulating dicer expression to activate dormant mouse blastocysts for implantation? summaryanswer:Let-7a post-transcriptionally regulates dicer expression altering microRNA expression to affect the implantation competency of the activated blastocysts. what is known already:The Let-7a microRNA is up-regulated during blastocyst dormancy and its forced-expression suppresses embryo implantationin vitro andin vivo. Dicer is a Let-7 target, which processes pre-microRNA to mature microRNA. study design, size, duration:The effects on the expression of Let-7a and dicer in dormant blastocysts during the first 12 h after estradiol-induced activation, and the relationship between Let-7a and dicer in preimplantation embryos were determined. The effects on the microRNAexpression and embryo implantationin vivoin dicer-knockdown mouse 5 –8 cell embryos and dormant blastocysts at 1 h post estradiol activation were also studied. participants/materials, setting, methods:ICR female mice at 6 weeks of age were ovariectomized on Day 4 of pregnancy to generate the delayed implantation model. Mouse 5–8 cell embryos and/or dormant blastocysts at 1 h after estradiol injection were electroporated with dicer siRNA and Let-7a precursor or Let-7a inhibitor. At 48 h post electroporation, the Let-7a expression, dicer transcripts and proteins in the embryos were determined using qPCR and immunostaining/western blotting, respectively. All experiments were repeated at least three times. main results and the role of chance:Estradiol injection down-regulated Let-7a and up-regulated dicer in the dormant blastocysts during the first 12 h post-activation. Dicer knockdown at 1 h post-activation of blastocysts suppressed EGFR expression, attenuated EGF binding and compromised implantation of the transferred embryos. Let-7a transcriptionally regulated dicer by binding to the 3 ′ -UTR of dicer in trophoblast cells. Dicer knockdown in blastocysts suppressed mature Let-7a expression and compromised implantation. limitations, reasons for caution:Gain- and loss-of-function approaches were used by analyzing transient expressions of transfected microRNA modulators or genes. The consequence of the Let-7a-dicer interaction on pregnancy remains to be determined. The study used the mouse as a model and the applicability of the observed phenomena in humans warrants further investigation. wider implications of the findings:Our results indicate that the Let-7a-dicer interaction leads to differential microRNA expression in dormant blastocysts after estradiol activation. Because the expression pattern of Let-7a in human blastocysts is similar to that in mouse blastocysts, our observation that the Let-7a-dicer interaction has a role in regulating the implantation potential of the mouse blastocysts could be applicable to humans.en_US
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://humrep.oxfordjournals.org/-
dc.relation.ispartofHuman Reproductionen_US
dc.subjectDicer-
dc.subjectDormant blastocyst-
dc.subjectEmbryo implantation-
dc.subjectEstradiol activation-
dc.subjectMicroRNA-
dc.titleMicroRNA Let-7a and dicer are important in the activation and implantation of delayed implanting mouse embryosen_US
dc.typeArticleen_US
dc.identifier.emailPang, RTK: rtkpang@hku.hken_US
dc.identifier.emailLiu, W: liuwm@hkucc.hku.hken_US
dc.identifier.emailLee, CKF: ckflee@hku.hken_US
dc.identifier.emailYeung, WSB: wsbyeung@hkucc.hku.hken_US
dc.identifier.authorityPang, RTK=rp01761en_US
dc.identifier.authorityLee, CKF=rp00458en_US
dc.identifier.authorityYeung, WSB=rp00331en_US
dc.identifier.doi10.1093/humrep/det462-
dc.identifier.pmid24419497-
dc.identifier.scopuseid_2-s2.0-84898990853-
dc.identifier.hkuros228592en_US
dc.identifier.volume29en_US
dc.identifier.issue4-
dc.identifier.spage750en_US
dc.identifier.epage762en_US
dc.identifier.isiWOS:000333051200014-
dc.publisher.placeUnited Kingdom-
dc.identifier.issnl0268-1161-

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