Of Micrornas Differentially Expressed During Rat Embryo Implantation And Regulation

Objective: To screen and identify differential expression of miRNAs in the rats uterus between pre-implantation period and implantation period. To research the expression and regulation of let-7a and miR-21 in the process of embryo implantation in rats. This study has the potential to provide new insights into the mechanisms of embryo implantation.Methods : MiRNAs microarray including 1256 miRNAs was used to examine differential expression of miRNAs in the rats uterus between pre-implantation period and implantation period, and partly differentially expressed miRNAs were identified by Northern blot. Northern blot and in situ hybridization was utilized to analyse expression and distribution of let-7a and miR-21 during peri-implantation period. Let-7a and miR-21 expression was detect in uterus of pseudopregnancy, artificial decidualization, delayed-implantation and ovariectomized rats treated with estradiol-17βor progesterone by Northern blot and in situ hybridization.Results:(1) Compared with pre-implantation period, there were 51 up-regulated and 61 down-regulated miRNAs at implantation period by miRNAs microarray. MiR-199a,miR-143,miR-29a,miR-126,miR-98,miR-10a,miR-352,miR-320,let-7a,miR-195,miR-16 and miR-21 confirmed by Northern blot were differential expression between pre-implantation period and implantation period.(2) The expression level of let-7a was higher during implantation in rats than during the pre-implantation and post-implantation periods. Let-7a was specifically localized in glandular and luminal epithelia and decidua. The expression of let-7a was not significantly different in the pseudopregnant uterus and increased significantly in the uteri of rats subjected to artificial decidualization and activation of delayed implantation. Treatment with estradiol-17βor progesterone significantly increased let-7a expression.(3) MiR-21 was differentially expressed in the rat uterus between pre-implantation period and implantation period. MiR-21 was specifically localized in the subluminal stromal cells and decidua. MiR-21 expression was not significantly different in uterus of pseudopregnancy, and significantly increased in the uterus of artificial decidualization and delayed-implantation. Treatment with estradiol-17βor progesterone downregulated miR-21 expression.Conclusion:(1) Differential expression of miRNAs was firstly screened and identified in the rats uterus between pre-implantation period and implantation period., which indicated that it play an important role in the rats uterus during embryo implantation.(2) Let-7a participate in embryo implantation in the early of pregnancy in rats. This increased expression level was mainly induced by active blastocysts and decidualization during the window of implantation. Steroid hormones, estradiol-17βor progesterone stimulated let-7a expression. Let-7a may play an important role during embroy implantation in the rats.(3) MiR-21 participate in embryo implantation in the early of pregnancy in rats. MiR-21 expression increase is mainly induced by blastocyst and participate in decidualization during the window of implantation, which may be beneficial to embryo implantation in the early of pregnancy in rats. Steroid hormones, estradiol-17βor progesterone inhibited miR-21 expression. MiR-21 may play an important role during embroy implantation in the rats.