Human Embryos Created by Embryo Splitting Secrete Significantly Lower Levels of miRNA-30c

Abstract

Studies reporting term pregnancy and the production of genetically identical offspring from isolated blastomeres of early stage embryos have been carried out in small and large animals. However, very little is known about the effects of embryo splitting on the development and reproductive competency of human embryos. In this study, we investigated the effects of embryo splitting on profile of microRNAs (miRNAs) detected in their spent blastocyst medium (SBM) by comparative analysis of miRNA profiles in SBM of human twin embryos created by blastomere biopsy and SBM of blastocysts that resulted in a healthy pregnancy and live birth following embryo transfer. The profile of miRNA secretion in in vitro culture media consistently distinguishes twin from control embryos. We found that six miRNAs are significantly more abundant in SBM from twin embryos, while nine are significantly more abundant in SBM from euploid implanted blastocysts. These nine include miRNA-30c, a previously reported marker of blastocyst implantation potential. Furthermore, 22.9% of miRNAs secreted by twin embryos were never detected in SBM from normal reproductively competent blastocysts, or from trophectoderm (TE) samples from normal blastocysts donated for the research. The miRNA profile, unique to twin blastocysts, might be a result of differential lineage commitment in these embryos.

Review: Embryo- and endometrium-derived exosomes and their potential role in assisted reproductive treatments–liquid biopsies for endometrial receptivity

“…The same group subsequently compared the profiles of 377 miR sequences in spent media from "twin" human blastocysts created by artificial embryo splitting at the cleavage stage with that of control blastocysts that produced healthy pregnancies [24]. They found 59 miRs secreted by control blastocysts and 48 miRs by twin embryos of which, only 22 were shared.…”

Bovine Embryo-Secreted microRNA-30c Is a Potential Non-invasive Biomarker for Hampered Preimplantation Developmental Competence

“…The delivery of miR-30c mimics to the MDBKs led to reduced cell proliferation and an arrest at G1 stage, while the delivery of miR-30c inhibitors resulted in the opposite effects, as expected. Previous studies on human embryos suggested that miR-30c can serve as a potential marker of blastocyst implantation potential (Capalbo et al, 2016; Noli et al, 2016). This is not surprising because although miR-30c is highly conserved between different species, it has been shown to act differently among different species.…”

Extracellular vesicle mediated embryo-endometrial cross talk during implantation and in pregnancy

“…Beyond the EVs, miRNAs have also been identified in culture media of human blastocysts and are detected in biopsied trophectoderm cells suggesting they are released from blastocysts [20][21][22][23][24]. While a formal proof that these miRNAs are EV-derived is yet awaited, since exosomes are enriched with miRNAs, it can be presumed that these blastocysts derived miRs could be secreted via MVs.…”