Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Modeling human embryo adhesion using a microfluidic platform

ABSTRACT: Single-cell RNA-seq dataset of models of human embryo adhesion in a microfluidic platform (ADOC). Embryo adhesion represents the first step of implantation, yet understanding this process has been hindered by the lack of human in vitro platforms that replicate endometrial physiology. Here, we present a dual-channel microfluidic platform containing organoid-derived endometrial epithelium and primary stromal cells. Our model recapitulates important endometrial hallmarks including epithelial polarization, stromal decidualization, extracellular vesicle release, and hormone-induced receptivity. We tested its function by introducing mouse and human blastocysts and showed that embryos displayed features of initial adhesion. These included establishment of embryo-epithelial contacts initiated via the polar trophectoderm, inner cell mass repositioning, and lineage segregation. Moreover, human embryos secreted βhCG indicating a functional trophoblast. Thus, this work provides a platform to study key features of embryo adhesion and endometrial receptivity, and disorders affecting embryo-endometrium interactions.

INSTRUMENT(S): Illumina NovaSeq X

ORGANISM(S): Homo sapiens

SUBMITTER: Carlos Simon

PROVIDER: E-MTAB-15842 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Endometrial receptivity plays a pivotal role in determining the success of embryo implantation and supports early pregnancy development, playing a central role in species propagation. However, current methods for assessing endometrial receptivity lack robust evidence-based validation, and reliable technique for accurately evaluating this process in patients with infertility are lacking. In this study, we introduced a novel patient-derived vascularised endometrium-on-a-chip (EoC) model, comprising three distinct layers, namely the epithelium, stroma, and blood vessels. This EoC was cross-species validated using both mouse and human samples, successfully replicating the dynamic microenvironment and mimicking both temporal and spatial features of the endometrial tissue. Using our EoC, we developed a clinically relevant endometrial receptivity scoring system, ERS², based on the molecular expression profiles of crucial endometrial receptivity markers and the morphological analyses of endometrial angiogenesis. The ERS² enables the personalised analysis of endometrial health and the potential for embryo implantation, addressing the individual variations in endometrial biology that may not be captured by traditional diagnostic methods. By leveraging our EoC, the ERS² replicate the physiological characteristics of the endometrium and provided personalised, patient-specific analyses. While larger-scale validation is required before clinical implementation, this highlights its significant potential for identifying therapeutic candidates tailored to individual patient, advancing the prospects for personalised reproductive care. Furthermore, progressive improvements in the patient’s endometrial microenvironment were observed following platelet-rich-plasma treatments, and the optimal timing for embryo transfer was identified in patients with unexplained repeated implantation failure using the EoC-ERS². This highlights the practical utility of our model not only for assessing individual receptivity but also for evaluating the personalised efficiency of interventions aimed at improving implantation outcomes. This study represents the first use of a microengineered EoC model and its scoring system to assess endometrial receptivity and predict successful pregnancy outcomes, offering new insights into personalised infertility treatments and advancing the potential of targeted therapies in reproductive medicine.

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Modeling human embryo adhesion using a microfluidic platform

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