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Dynamic of intrauterine crosstalk promotes embryo implantation in early pregnancy

ABSTRACT: The success of early pregnancy depends largely on the successful implantation of the embryo. Dynamic crosstalk between embryo and mother plays a crucial role in this process, but our understanding is still limited. Here, using the pig as a model, we first comprehensively profile the single-cell transcriptome of early free embryos and corresponding maternal endometrium, identifying embryonic and matched endometrial cells with heterogeneity. We developed a novel tool, ExtraCellTalk, to predict crosstalk between the early embryo and the maternal uterus using uterine luminal proteins as bridges, generating an overall dynamic map of maternal-fetal crosstalk. Through cross-species comparisons, we identified a conserved RBP4/STRA6 pathway in which embryonic-derived RBP4 targets the STRA6 receptor on stromal cells in the endometrium, thereby interacting with endothelial and perivascular cells to regulate their interconversion to promote endometrial remodeling. These maternal-fetal crosstalks and corresponding endometrial changes that we uncovered are essential for subsequent embryo implantation and are the basis for further studies to improve embryo implantation.

ORGANISM(S): Sus scrofa

PROVIDER: GSE222544 | GEO | 2025/01/01

REPOSITORIES: GEO

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Project description:The developmental origins of adult disease are now recognized to reflect intrauterine conditions during embryonic and fetal life. Cell-cell communication between the maternal endometrium and the pre-implantation embryo can occur by several means. Here, we show that maternal miRNAs are secreted by the endometrial epithelium to the endometrial fluid. Microarray assessments revealed the presence of specific miRNAs that are associated with the window of implantation and therefore in direct contact with the human preimplantation embryo. These miRNAS are transported as free or exosome-associated molecules secreted to the endometrial fluid and then uptake into the pre-implantation embryo through the trophoectoderm. Finally, these maternal miRNAs were able to induce transcriptional and functional modifications of the embryo. Therefore, we propose an innovative model whereby endometrial maternal miRNAS may function as transcriptomic regulators during early embryo development offering a new perspective on the developmental origins of adult diseases such as obesity, type 2 diabetes, and others that are now recognized to reflect intrauterine conditions. The B6C3F1 mice strain was purchased. Female mice aged 6M-bM-^@M-^S8 weeks were primed to ovulate by administering 10 IU pregnant mare serum gonadotropin(Sigma-Aldrich, Irvine, UK), followed by administration of 10 IU hCG(Sigma-Aldrich, Irvine, UK), 48 hours later. Females were housed overnight with male breeders and examined the following morning for the presence of a vaginal plug (day 1 of pregnancy). On day 2 of pregnancy, mice were sacrificed by cervical dislocation, and embryos flushed with PBS from the oviduct using a blunt 30-gauge needle. Then, embryos were cultured in CCM-30 medium (Vitrolife, Lubeck, Germany) in presence or absence of 400nM of mir-30d MIMIC or Scramble-Alexa 488 for 72 hours. Then embryos are four times washed in fresh CCM. Experiment were carried out by triplicate and with 30 embryos/condition

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Dynamic of intrauterine crosstalk promotes embryo implantation in early pregnancy

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