Spatial-temporal regulation of the prostanoid receptor EP2 co-ordinates PGE2-mediated cAMP signaling in decidualizing human endometrium.

Decidualization denotes the differentiation of endometrial stromal cells into specialized decidual cells, essential for embryo implantation and pregnancy. The process requires coordination of progesterone and cAMP signaling, which converge on downstream transcription factors. PGE2 and relaxin, acting, respectively, through Gαs-coupled GPCRs EP2 and RXFP1, are putative candidates for generating cAMP in differentiating stromal cells.

Dynamic chromatin remodeling in cycling human endometrium at single-cell level.

Estrogen-dependent proliferation followed by progesterone-dependent differentiation of the endometrium culminates in a short implantation window. We performed single-cell assay for transposase-accessible chromatin with sequencing on endometrial samples obtained across the menstrual cycle to investigate the regulation of temporal gene networks that control embryo implantation. We identify uniquely accessible chromatin regions in all major cellular constituents of the endometrium, delineate temporal patterns of coordinated chromatin remodeling in epithelial and stromal cells, and gain mechanistic insights into the emergence of a receptive state through integrated analysis of enriched transcription factor (TF) binding sites in dynamic chromatin regions, chromatin immunoprecipitation sequencing analyses, and gene expression data.

Lineage skewing and genome instability underlie marrow failure in a zebrafish model of GATA2 deficiency.

Inherited bone marrow failure associated with heterozygous mutations in GATA2 predisposes toward hematological malignancies, but the mechanisms remain poorly understood. Here, we investigate the mechanistic basis of marrow failure in a zebrafish model of GATA2 deficiency. Single-cell transcriptomics and chromatin accessibility assays reveal that loss of gata2a leads to skewing toward the erythroid lineage at the expense of myeloid cells, associated with loss of cebpa expression and decreased PU.

MicroRNAs emerging coordinate with placental mammals alter pathways in endometrial epithelia important for endometrial function.

We tested the hypothesis that conserved placental mammal-specific microRNAs and their targets facilitate endometrial receptivity to implantation. Expression of miR-340-5p, -542-3p, and -671-5p was regulated by exposure of endometrial epithelial cells to progesterone (10 μg/ml) for 24 h coordinate with 1,713 of their predicted targets. Proteomic analysis of cells transfected with miRNA mimic/inhibitor (48 h: n = 3) revealed 1,745 proteins altered by miR-340-5p (mimic; 1,369, inhibitor; 376) of which 171 were predicted targets and P4-regulated.

EndoTime: non-categorical timing estimates for luteal endometrium.

Study Question: Can the accuracy of timing of luteal phase endometrial biopsies based on urinary ovulation testing be improved by measuring the expression of a small number of genes and a continuous, non-categorical modelling approach?

Summary Answer: Measuring the expression levels of six genes (IL2RB, IGFBP1, CXCL14, DPP4, GPX3 and SLC15A2) is sufficient to obtain substantially more accurate timing estimates and to assess the reliability of timing estimates for each sample.

What Is Known Already: Commercially available endometrial timing approaches based on gene expression require large gene sets and use a categorical approach that classifies samples as pre-receptive, receptive or post-receptive.

Study Design, Size, Duration: Gene expression was measured by RTq-PCR in different sample sets, comprising a total of 664 endometrial biopsies obtained 4-12 days after a self-reported positive home ovulation test.