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Biology subjects

Santamaria, X.

Publications and source records attributed to Santamaria, X..

2 recordsLinked to original sources

Modeling human embryo adhesion using a microfluidic platform

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 {beta}hCG 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. TeaserEndometrium-on-a-chip shows detailed human embryo adhesion dynamics.

molecular biology↗

Global Endometrial DNA Multi-omics Analysis Reveals Insights into mQTL Regulation and Associated Endometriosis Disease Risk

Endometriosis is a leading cause of pain and infertility affecting millions of women globally. Identifying biologic and genetic effects on DNA methylation (DNAm) in endometrium increases understanding of mechanisms that influence gene regulation predisposing to endometriosis and offers an opportunity for novel therapeutic target discovery. Herein, we characterize variation in endometrial DNAm and its association with menstrual cycle phase, endometriosis, and genetic variants through analysis of genome-wide genotype data and methylation at 759,345 DNAm sites in endometrial samples from 984 deeply-phenotyped participants. We identify significant differences in DNAm profiles between menstrual cycle phases and at four DNAm sites between stage III/IV endometriosis and controls. We estimate that 15.4% of the variation in endometriosis is captured by DNAm, and identify DNAm networks associated with endometriosis. DNAm quantitative trait locus (mQTL) analysis identified 118,185 independent cis-mQTL including some tissue-specific effects. We find significant differences in DNAm profiles between endometriosis sub- phenotypes and a significant association between genetic regulation of methylation in endometrium and disease risk, providing functional evidence for genomic targets contributing to endometriosis risk and pathogenesis.

systems biology↗