Unknown,Transcriptomics,Genomics,Proteomics

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Transcriptomic of early embryonic invasion at implantation sites in a murine model.

ABSTRACT: Trophoblast Invasion is a complex mechanism that involves several genes and processes that are exquisitely regulated by the mother. Functional genomics has shown that immunomodulatory and proliferation are two essential key processes involved. Adult virgin B6CBA F1/J female mice were mated with CD1 fertile males to induce pregnancy (day 0=vaginal plug). Mice were sacrificed by cervical dislocation. Implantation and inter-implantation sites were divided by sharp dissection 6.5 days post-coitum (dpc) (n=3 mice). Uterine segments included uterine myometrium, stroma, and epithelium. Inter-implantation decidua (ID) were collected and Implantation sites also were divided by sharp dissection to separate extra-embryonic tissue (ET) from surrounding decidua (SD). From the embryo, only the invasive trophoblast formed by the ectoplacental cone was studied too.

ORGANISM(S): Mus musculus

SUBMITTER: Juan Moreno-Moya

PROVIDER: E-GEOD-46732 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Prior to pregnancy, hormonal changes lead to cellular adaptations in the endometrium allowing for embryo implantation. Critical for successful pregnancy establishment, innate immune cells constitute a significant proportion of uterine cells prior to arrival of the embryo and throughout the first trimester in humans and animal models. Abnormal uterine immune cell function during implantation is believed to play a role in multiple adverse pregnancy outcomes. Current work in humans has focused on uterine immune cells present after pregnancy establishment, and limited in vitro models exist to explore unique functions of these cells. With single-cell RNA-sequencing (scRNAseq), we comprehensively compared the human uterine immune landscape of the endometrium during the window of implantation and the decidua during the first trimester of pregnancy. We uncovered global and cell-type-specific gene signatures for each timepoint. Immune cells in the endometrium prior to implantation expressed genes associated with immune metabolism, division, and activation. In contrast, we observed widespread interferon signaling during the first trimester of pregnancy. We also provide evidence of specific inflammatory pathways enriched in pre- and post-implantation macrophages and natural killer (NK) cells in the uterine lining. Using our novel implantation-on-a-chip (IOC) to model human implantation ex vivo, we demonstrate for the first time that uterine macrophages strongly promote invasion of extravillous trophoblasts (EVTs), a process essential for pregnancy establishment. Pre- and post-implantation uterine macrophages promoted EVT invasion to a similar degree as pre- and post-implantation NK cells on the IOC. This work provides a foundation for further investigation of the individual roles of uterine immune cell subtypes present prior to embryo implantation and during early pregnancy, which will be critical for our understanding of pregnancy complications associated with abnormal trophoblast invasion and placentation.

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Transcriptomic of early embryonic invasion at implantation sites in a murine model.

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