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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
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
2015 Impact Factor: 4.621
2015 SCImago Journal Rankings: 2.271
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.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.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-

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