Human Endometrial Transcriptome and Progesterone Receptor Cistrome Reveal Important Pathways and Epithelial Regulators

Chi, Alicia; Wang, Tianyuan; Adams, Nyssa; Wu, San‐Pin; Young, Steven L.; Spencer, Thomas E.; DeMayo, Francesco J.

doi:10.1101/680181

Cited by 11 publications

(18 citation statements)

References 101 publications

(90 reference statements)

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“…PR-A and PR-B form homodimers or heterodimers [ 85 ], and PR-A exerts dominant negative effects on PR-B mediated transcription [ 86 ]. ChIP-seq analyses of human endometrium [ 87 ] and mouse uterus and ovary [ 88 ] revealed that PRs exert genomic action by binding progesterone response elements (PREs) or other transcription factor binding motifs. Nongenomic effects of PRs are also reported, which are mediated by the interaction of a proline-rich sequence motif within PRs and SRC homology 3 (SH3) domain in Src family tyrosine kinases leading to the activation of Src family tyrosine kinases [ 89 ].…”

Section: Prs In the Regulation Of Mitochondrial Oxphos Complexesmentioning

confidence: 99%

Mechanisms Underlying the Regulation of Mitochondrial Respiratory Chain Complexes by Nuclear Steroid Receptors

Kobayashi

Azuma

Ikeda

et al. 2020

IJMS

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Mitochondrial respiratory chain complexes play important roles in energy production via oxidative phosphorylation (OXPHOS) to drive various biochemical processes in eukaryotic cells. These processes require coordination with other cell organelles, especially the nucleus. Factors encoded by both nuclear and mitochondrial DNA are involved in the formation of active respiratory chain complexes and ‘supercomplexes’, the higher-order structures comprising several respiratory chain complexes. Various nuclear hormone receptors are involved in the regulation of OXPHOS-related genes. In this article, we review the roles of nuclear steroid receptors (NR3 class nuclear receptors), including estrogen receptors (ERs), estrogen-related receptors (ERRs), glucocorticoid receptors (GRs), mineralocorticoid receptors (MRs), progesterone receptors (PRs), and androgen receptors (ARs), in the regulatory mechanisms of mitochondrial respiratory chain complex and supercomplex formation.

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Section: Prs In the Regulation Of Mitochondrial Oxphos Complexesmentioning

confidence: 99%

Mechanisms Underlying the Regulation of Mitochondrial Respiratory Chain Complexes by Nuclear Steroid Receptors

Kobayashi

Azuma

Ikeda

et al. 2020

IJMS

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“…The molecular protagonists in the decidualization route are P4 and cAMP [29]. The PGR-regulated genes and pathways include HOXA10, HAND2, IGFBP-1, and BMP2; ERK/MAPK, WNT/ß-catenin, and IHH-COUPTFII pathways [35]. HOXA10 is a PGR target in the endometrium and has been reported to in uence WNT4 expression around the implantation site in mice [36].…”

Section: Wnt/ß-catenin Signaling Pathwaymentioning

confidence: 99%

DNA Methylation Changes in Endometrium and Correlation with Gene Expression During Ovarian Hyper-stimulation

Sun¹,

Ma²,

Wang³

et al. 2020

Preprint

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Persistent supraphysiological serum estradiol (E2) levels during controlled ovarian hyper-stimulation (COH) have a detrimental effect on endometrial receptivity. In this study, we explored RNA expression and DNA methylation profiles from patients’ endometrium. The patients were divided into two groups: the COH cycle (n=3, hCG+7) group and normal cycle group (n=3, LH+5). Quantitative RT-PCR was used to validate the expression of selected differentially expressed genes (DEGs). Comparing natural and stimulated endometrium transcriptome profiles revealed 640 DEGs, with a > 2-fold change (FC) and p < 0.01. The DEGs were reported to be involved in endometrial receptivity and epithelial-mesenchymal transition (EMT). The expression of IGFBP-1, MMP9, FGF9, LIF, WNT4, HAND2, and immune system-related genes were significantly up-regulated. By clustering and KEGG pathway analysis, molecules and pathways associated with endometrial receptivity (PI3K-Akt signaling pathway) were identified. DNA methylation was partially correlated to gene expression. In conclusion, RNA-seq COH affected endometrial receptivity and EMT/MET process by accelerated the decidualization process and broken the balance of estrogen and progesterone receptors expression. However, this was not associated with changes in DNA methylation.

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“…To identify the gene networks functioning at the TE-EEC interface, we used single-cell transcriptomic datasets from blastocyst TE (Petropoulos et al 2016), and bulk transcriptomic data from EEC directly isolated from endometrium (Chi et al 2020). Cell surface or secreted genes, differentially expressed in receptive (mid-secretory phase) vs non-receptive (proliferative phase) endometrial epithelium ( Figure S2A), were used to identify 39 cognate cell surface genes in day 6 TE.…”

Section: Gene Network At the Te-eec Interfacementioning

confidence: 99%

“…All in silico modelling and analysis was performed in R version 3.4.2 (R Foundation for Statistical Computing). Differentially expressed genes (DEGs) were defined by ANOVA (cutoff p<0.01) between proliferative phase (n=4) and mid-secretory phase (n=4) endometrial epithelial RNA sequencing (RNAseq) transcriptomes (GEO Accession GSE132711) (Chi et al 2020). Localisation of the protein products of these genes was investigated using the Database for Annotation, Visualisation and Integrated Discovery (DAVID) (Huang da et al 2009a, Huang da et al 2009b.…”

Section: Modelling the Te-eec Interface In Silicomentioning

confidence: 99%

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Trophectoderm differentiation to invasive syncytiotrophoblast is induced by endometrial epithelial cells during human embryo implantation

Ruane¹,

Garner²,

Parsons

et al. 2020

Preprint

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At implantation, trophoblast derived from the trophectoderm of the blastocyst-stage embryo invades the endometrium to establish pregnancy. To understand how embryos breach the endometrial epithelium, we modelled human implantation using blastocysts or trophoblast stem cell spheroids cultured with endometrial epithelial cells (EEC). Blastocyst invasion of the EEC layer was initiated by multinuclear syncytiotrophoblast. Spheroids also invaded the epithelium with syncytiotrophoblast, and EEC induced upregulation of syncytiotrophoblast markers. Modelling implantation in silico using blastocyst and EEC transcriptomes revealed gene networks that exhibited greater connectivity and organisation in trophectoderm of the polar region of the embryonic axis. However, gene ontologies and machine learning suggested that EEC drives syncytiotrophoblast differentiation in polar and mural trophectoderm. This is the first evidence for endometrial epithelium-induced trophectoderm differentiation to invasive syncytiotrophoblast as the cellular mechanism of embryonic breaching of the endometrium in humans, with implications for reproductive medicine and our understanding of human embryonic development.

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Human Endometrial Transcriptome and Progesterone Receptor Cistrome Reveal Important Pathways and Epithelial Regulators

Abstract: 1 9 2 0

Cited by 11 publications

References 101 publications

Mechanisms Underlying the Regulation of Mitochondrial Respiratory Chain Complexes by Nuclear Steroid Receptors

Mechanisms Underlying the Regulation of Mitochondrial Respiratory Chain Complexes by Nuclear Steroid Receptors

DNA Methylation Changes in Endometrium and Correlation with Gene Expression During Ovarian Hyper-stimulation

Trophectoderm differentiation to invasive syncytiotrophoblast is induced by endometrial epithelial cells during human embryo implantation

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