Hsa-miR-30d, secreted by the human endometrium, is taken up by the pre-implantation embryo and might modify its transcriptome

Abstract

During embryo implantation, the blastocyst interacts with and regulates the endometrium, and endometrial fluid secreted by the endometrial epithelium nurtures the embryo. Here, we propose that maternal microRNAs (miRNAs) might act as transcriptomic modifier of the pre-implantation embryo. Microarray profiling revealed that six of 27 specific, maternal miRNAs were differentially expressed in the human endometrial epithelium during the window of implantation -a brief phase of endometrial receptivity to the blastocyst -and were released into the endometrial fluid. Further investigation revealed that hsa-miR-30d, the expression levels of which were most significantly upregulated, was secreted as an exosome-associated molecule. Exosome-associated and free hsa-miR-30d was internalized by mouse embryos via the trophectoderm, resulting in an indirect overexpression of genes encoding for certain molecules involved in the murine embryonic adhesion phenomenon -Itgb3, Itga7 and Cdh5. Indeed, this finding was supported by evidence in vitro: treating murine embryos with miR-30d resulted in a notable increase in embryo adhesion. Our results suggest a model in which maternal endometrial miRNAs act as transcriptomic modifiers of the preimplantation embryo.

Inhibition of Fatty Acid Synthase Reduces Blastocyst Hatching through Regulation of the AKT Pathway in Pigs

“…miRNAs are non-coding RNAs that regulate many biological processes, including embryonic development [39–42]. miRNAs play an important role in the maternal-conceptus interface[43].…”

Embryo–epithelium interactions during implantation at a glance

“…The encapsulated miRs include Hsa-miR-30d, which targets a group of adhesion molecules in the blastocyst and increases the levels of integrins β3 and α7, and cadherin 5. Accordingly, embryos that express miR-30d display increased adhesion to epithelial cells in vitro (Vilella et al, 2015). By contrast, there is evidence that a skewed miR profile in epithelial cells can impair receptivity (Kang et al, 2015).…”

Extracellular Vesicles in the Intrauterine Environment: Challenges and Potential Functions

“…Extracellular vesicles have been identified in vivo in body fluids, including amniotic fluid, urine, and blood, and isolated from uterine fluid in sheep and women [18, 20, 21, 43, 44]. Furthermore, recent publications have demonstrated that EVs are released from human endometrial epithelial cells [18, 37, 44–46], extravillous and villous trophoblast cells [47], and primary trophoblast from term placenta [44, 48]. …”