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Podocalyxin governs the barrier function of human endometrial epithelium and critically regulates receptivity for embryo implantation

ABSTRACT: Podocalyxin governs the barrier function of human endometrial epithelium and critically regulates receptivity for embryo implantation

PROVIDER: PRJNA623636 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11506600.fastq.gz	Fastqsanger.gz
	SRR11506601.fastq.gz	Fastqsanger.gz
	SRR11506594.fastq.gz	Fastqsanger.gz
	SRR11506595.fastq.gz	Fastqsanger.gz
	SRR11506596.fastq.gz	Fastqsanger.gz

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Podocalyxin governs the barrier function of human endometrial epithelium and critically regulates receptivity for embryo implantation

Project description:Embryo implantation is a key step in establishing pregnancy and a major limiting factor in IVF. Implantation requires the endometrium, the inner lining of the uterus, to transform from a non-receptive to a receptive state, to allow embryos to attach to the surface and enter into the tissue. However, the fundamental mechanisms governing receptivity are not well understood. Here we show that transmembrane protein podocalyxin is a major and clinically significant factor regulating human endometrial receptivity. Podocalyxin is expressed in all endometrial epithelial cells in the non-receptive state but is selectively down-regulated in the luminal epithelium at receptivity. We present evidence that podocalyxin critically governs the barrier function of the endometrial epithelium, likely as an intrinsic protective mechanism, rendering it non-receptive to an embryo. In addition, podocalyxin suppresses genes promoting receptivity (eg LIF, CSF1) but stimulates those inhibiting implantation (eg WNT7A, LEFTY2). Down-regulation of podocalyxin in the luminal epithelium, likely mediated by progesterone, selectively converts the endometrial surface to a more adhesive state that facilitates embryo attachment and penetration. Furthermore, inadequate down-regulation of podocalyxin in the endometrial luminal epithelium is associated with poorer implantation rates in IVF. We thus propose that podocalyxin promotes the barrier function of human endometrial epithelial cells and critically regulates receptivity for embryo implantation.

2021-04-01 | GSE148274 | GEO

Enhancing Uterine Receptivity for Embryo Implantation through Controlled Collagenase Intervention

Project description:Ineffective endometrial matrix remodeling, a key factor in infertility, impedes embryo implantation in the uterine wall. Our study reveals the cellular and molecular impact of human collagenase-1 administration in mouse uteri, demonstrating enhanced embryo implantation rates. Collagenase-1 promotes remodeling of the endometrial extracellular matrix (ECM), degrading collagen fibers and proteoglycans. This process releases matrix-bound bioactive factors, (e.g. VEGF, decorin), facilitating vascular permeability and angiogenesis. Collagenase-1 elevates embryo implantation regulators, including NK cell infiltration and the key cytokine LIF. Remarkably, uterine tissue maintains structural integrity despite reduced endometrial collagen fiber tension. In-utero collagenase-1 application rescues implantation in the heat stress and embryo transfer models, known for low implantation rates. Importantly, ex-vivo exposure of human uterine tissue to collagenase-1 induces collagen de-tensioning and VEGF release, mirroring remodeling observed in mice. Our research highlights collagenase potential to induce and orchestrate cellular and molecular processes enhancing uterine receptivity for effective embryo implantation. This innovative approach underscores ECM remodeling mechanisms critical for embryo implantation

2024-08-13 | PXD054389 | Pride

Gene expression study of human endometrial receptivity in IVF implantation failure patients undergoing ovarian stimulation

Project description:Endometrial receptivity on genomic level is one of the major cause of implantation failure in IVF patients with unexlained infertility and is a main obstacle in success of IVF. Gene expression profiles of implantation failure cases of unexplained infertility were compared with proven healthy oocyte donors as controls, both undergoing ovarian stimulation. The results provide additional information about gene expression profile related to endometrial receptivity in implantation failure cases especially under the influence of ovarian stimulation during IVF cycle.

2018-08-07 | GSE71835 | GEO

Gene expression study of human endometrial receptivity in IVF implantation failure patients undergoing ovarian stimulation II

Project description:Endometrial receptivity on genomic level is one of the major cause of implantation failure in IVF patients with unexplained infertility and is a main obstacle in success of IVF. Gene expression profiles of implantation failure cases of unexplained infertility were compared with proven healthy oocyte donors as controls, both undergoing ovarian stimulation. The results provide additional information about gene expression profile related to endometrial receptivity in implantation failure cases especially under the influence of ovarian stimulation during IVF cycle.

2019-06-25 | GSE92324 | GEO

Uterine glands impact uterine receptivity, luminal fluid homeostasis and blastocyst implantation

Project description:Uterine glands are essential for pregnancy in mice and likely humans, because they secrete or transport bioactive substances that regulate uterine receptivity for blastocyst implantation. In mice, the uterus becomes receptive to blastocyst implantation on day 4, but is refractory by day 5. Here, blastocysts could be recovered from progesterone-induced uterine gland (PUGKO) but not wildtype (WT) mice on day 5 post-mating. Anti-adhesive Muc1 protein and microvilli were present on the luminal epithelium of PUGKO but not WT uteri. A number of known uterine receptivity genes and gland-specific genes were altered in the PUGKO uterus. Next, the uterus and uterine luminal fluid (ULF) were obtained from WT and PUGKO mice on day 3, 4 and 5. Transcriptome analysis revealed that 580 genes were decreased in the PUGKO uterus, however ULF secrotome analysis revealed that many proteins and several amino acids were increased in the PUGKO ULF. Of note, many proteins encoded by many gland-specific genes were not identified in the ULF of WT mice. These results support the ideas that uterine glands secrete factors that regulate ULF homeostasis and interact with other cell types in the uterus to influence uterine receptivity and blastocyst implantation for the establishment of pregnancy.

2016-11-22 | GSE90101 | GEO

The endometrial trasccriptome transition accompanying acquisition of receptivity to embryo implantation in mice

Project description:Receptivity of the uterus is essential for embryo implantation and progression of pregnancy. Acquisition of receptivity involves major molecular and cellular changes in the endometrial lining of the uterus from its non-receptive state at ovulation, to its receptive state four days later. The precise molecular mechanisms underlying this transition remain to be fully characterized. Here, we aimed to generate a comprehensive profile of the uterine transcriptome in the peri-ovulatory and peri-implantation states, and to define the differences between them, in the mouse. High throughput RNA-sequencing was utilized to identify genes and pathways expressed in the endometrium of C57Bl/6 female mice on day 3.5 post-coitum after mating with BALB/c males, compared to the endometrium of unmated estrous females (n=3-4 biological replicates). RNA-sequencing and analysis using Ingenuity Pathway Analysis software revealed that, compared to the endometrium at estrus, 388 genes were differentially expressed in the endometrium on day 3.5 post-coitum (FDR ≤ 0.05). Several upstream regulators are implicated in the transition to receptivity including several cytokines, steroid hormones, prostaglandin E2, and vascular endothelial growth factor A. The transcriptional changes indicate substantial changes in the uterine immune and vascular systems during the pre-implantation phase, with the functional terms Angiogenesis, Chemotaxis, and Lymphangiogenesis predominating. This analysis confirms that the transcriptome of a receptive uterus is vastly different to the non-receptive uterus and identifies several genes and regulatory pathways not previously associated with implantation. This dataset will serve as a valuable tool and resource for future research on the molecular mechanisms of uterine receptivity.

2023-09-12 | GSE223136 | GEO

Unveiling the Molecular Mechanisms of ligustilide in Enhancing Endometrial Receptivity

Project description:Endometrial receptivity (ER) refers to the ability of the endometrium to accept embryos in the window of implantation during which the endometrial tissue allows embryo implantation and pregnancy initiation. In women with certain gynecological diseases, including polycystic ovary syndrome, tubal disease and endometriosis, ER appears to be impaired, leading to infertility and pregnancy failure. Ligustilide (LIG) treatment can restore endometrial receptivity and promote implantation in pregnant rats with low endometrial receptivity (LER). However, the mechanism by which LIG affects LER is unknown. In the current study,we conducted a bioinformatic analysis of endometrial tissues of rats with NER, LER, and LIG-treated LER.

2025-07-03 | GSE301071 | GEO

Dysregulated microRNAs in uterine fluid from women with recurrent implantation failure are linked to endometrial receptivity and implantation

Project description:Dysregulated microRNAs in uterine fluid from women with recurrent implantation failure are linked to endometrial receptivity and implantation

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