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Conference Paper: Up-regulation of Lin28 and Dicer Are Required for the Activation of Mouse Blastocysts

TitleUp-regulation of Lin28 and Dicer Are Required for the Activation of Mouse Blastocysts
Authors
Issue Date2013
PublisherThe Society for the Study of Reproduction (SSR).
Citation
The 46th Annual Meeting of Society for the Study of Reproduction (SSR 2013), Montréal, Québec, Canada, 22–26 July 2013. In Conference Program, 2013, p. 292, abstract no. 640 How to Cite?
AbstractMicroRNA Let-7 family is down-regulated during the pre-implantation embryo development and upon estradiol-activation of the dormant blastocysts. Induction of Let-7a in mouse blastocysts attenuates trophoblast attachment and outgrowth in vitro and compromises pregnancy in vivo partly via modulation of the expression of integrin beta-3 and Vav3. However, the mechanism that regulates Let-7a expression in mouse blastocysts remains unknown. It is known that Let-7 expression is regulated by Dicer and Lin28 (Lin28A and Lin28B) in other cell types. Dicer is a RNAase III enzyme that cleaves precursor microRNAs into their mature form. The RNA-binding protein Lin28 is a negative regulator of Let-7. It recruits the TUTases to assemble the Ago-mediated microRNA degradation complex. Although Dicer and Lin28 modulate Let-7a expression, they are putative targets of Let-7a. In this study, we hypothesized that Dicer and Lin28 were mediators of Let-7a action upon blastocyst activation. During pre-implantation development towards blastocysts, the expression of primary and mature Let-7a in embryos decreased, while that of Lin28 and Dicer increased. Force-expression of Let-7a inhibited Dicer and Lin28 protein expression in the blastocysts. In the dormant mouse blastocyst, Let-7a expression was high. Estradiol adminstration down-regulated Let-7a expression, but upregulated that of the dicer protein in the these blastocysts. Knockdown of dicer at one-hour post-estradiol activation led to a shift of the microRNAome towards that of the dormant blastocysts, and repressed implantation in vivo and in vitro as indicated by a decrease in epidermal growth factor binding ability. Similarly, Lin28 was up-regulated along the mural trophectoderm of the dormant blastocysts after 3-hour post estradiol activation. The temporal change in Lin28 expression among the estradiol activated dormant blastocysts was yet lagged from that of dicer. Knocking down of Lin28 at one-hour post estradiol activation increased the mature Let-7a expression and concurrently lowered the implantation rate in vivo. The data thus supported that during activation of dormant blastocyst, the down-regulation of Let-7a enhanced Dicer expression for microRNA processing, and Lin28 expression, which degraded the primary and mature Let-7a to potentiate implantation. [The research work is partly supported by a GRF grant to WSBY].
DescriptionConference Theme: Reproductive Health: Nano to Global
Persistent Identifierhttp://hdl.handle.net/10722/190480

 

DC FieldValueLanguage
dc.contributor.authorCheong, WYAen_US
dc.contributor.authorPang, RTKen_US
dc.contributor.authorLiu, Wen_US
dc.contributor.authorLee, CKFen_US
dc.contributor.authorYeung, WSBen_US
dc.date.accessioned2013-09-17T15:24:11Z-
dc.date.available2013-09-17T15:24:11Z-
dc.date.issued2013en_US
dc.identifier.citationThe 46th Annual Meeting of Society for the Study of Reproduction (SSR 2013), Montréal, Québec, Canada, 22–26 July 2013. In Conference Program, 2013, p. 292, abstract no. 640en_US
dc.identifier.urihttp://hdl.handle.net/10722/190480-
dc.descriptionConference Theme: Reproductive Health: Nano to Global-
dc.description.abstractMicroRNA Let-7 family is down-regulated during the pre-implantation embryo development and upon estradiol-activation of the dormant blastocysts. Induction of Let-7a in mouse blastocysts attenuates trophoblast attachment and outgrowth in vitro and compromises pregnancy in vivo partly via modulation of the expression of integrin beta-3 and Vav3. However, the mechanism that regulates Let-7a expression in mouse blastocysts remains unknown. It is known that Let-7 expression is regulated by Dicer and Lin28 (Lin28A and Lin28B) in other cell types. Dicer is a RNAase III enzyme that cleaves precursor microRNAs into their mature form. The RNA-binding protein Lin28 is a negative regulator of Let-7. It recruits the TUTases to assemble the Ago-mediated microRNA degradation complex. Although Dicer and Lin28 modulate Let-7a expression, they are putative targets of Let-7a. In this study, we hypothesized that Dicer and Lin28 were mediators of Let-7a action upon blastocyst activation. During pre-implantation development towards blastocysts, the expression of primary and mature Let-7a in embryos decreased, while that of Lin28 and Dicer increased. Force-expression of Let-7a inhibited Dicer and Lin28 protein expression in the blastocysts. In the dormant mouse blastocyst, Let-7a expression was high. Estradiol adminstration down-regulated Let-7a expression, but upregulated that of the dicer protein in the these blastocysts. Knockdown of dicer at one-hour post-estradiol activation led to a shift of the microRNAome towards that of the dormant blastocysts, and repressed implantation in vivo and in vitro as indicated by a decrease in epidermal growth factor binding ability. Similarly, Lin28 was up-regulated along the mural trophectoderm of the dormant blastocysts after 3-hour post estradiol activation. The temporal change in Lin28 expression among the estradiol activated dormant blastocysts was yet lagged from that of dicer. Knocking down of Lin28 at one-hour post estradiol activation increased the mature Let-7a expression and concurrently lowered the implantation rate in vivo. The data thus supported that during activation of dormant blastocyst, the down-regulation of Let-7a enhanced Dicer expression for microRNA processing, and Lin28 expression, which degraded the primary and mature Let-7a to potentiate implantation. [The research work is partly supported by a GRF grant to WSBY].-
dc.languageengen_US
dc.publisherThe Society for the Study of Reproduction (SSR).-
dc.relation.ispartofAnnual Meeting of Society for the Study of Reproduction, SSR 2013en_US
dc.titleUp-regulation of Lin28 and Dicer Are Required for the Activation of Mouse Blastocystsen_US
dc.typeConference_Paperen_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.hkuros222567en_US
dc.identifier.spage292, abstract no. 640-
dc.identifier.epage292, abstract no. 640-
dc.publisher.placeUnited States-

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