• Ana W Y Cheong, Ronald T K Pang, Wei-Min Liu, Kottawattage Sanda Arunika Kottawatta, Kai-Fai Lee, and William S B Yeung.
• Department of Obstetrics and Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
• Hum. Reprod. 2014 Apr 1; 29 (4): 750-62.

Study QuestionDoes Let-7a have a functional role in modulating dicer expression to activate dormant mouse blastocysts for implantation?Summary AnswerLet-7a post-transcriptionally regulates dicer expression altering microRNA expression to affect the implantation competency of the activated blastocysts.What Is Known AlreadyThe Let-7a microRNA is up-regulated during blastocyst dormancy and its forced-expression suppresses embryo implantation in vitro and in vivo. Dicer is a Let-7 target, which processes pre-microRNA to mature microRNA.Study Design, Size, DurationThe 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 microRNA expression and embryo implantation in vivo in dicer-knockdown mouse 5-8 cell embryos and dormant blastocysts at 1 h post estradiol activation were also studied.Participants/Materials, Setting, MethodsICR 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 ChanceEstradiol 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 CautionGain- 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 FindingsOur 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.Study Funding/Competing Interest(S)This project is supported partly by a research grant from the Research Grant Council to W.S.B.Y. The authors have no competing interests to declare.

33 keywords...

hide…