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METTL3-dependent m6A methylation facilitates uterine receptivity and female fertility via balancing estrogen and progesterone signaling

ABSTRACT: METTL3-dependent m6A methylation facilitates uterine receptivity and female fertility via balancing estrogen and progesterone signaling

PROVIDER: PRJNA858272 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20139751_1.fastq.gz	Fastqsanger.gz
	SRR20139751_2.fastq.gz	Fastqsanger.gz
	SRR20139752_1.fastq.gz	Fastqsanger.gz
	SRR20139752_2.fastq.gz	Fastqsanger.gz
	SRR20139753_1.fastq.gz	Fastqsanger.gz

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METTL3-dependent m6A methylation facilitates uterine receptivity and female fertility via balancing estrogen and progesterone signaling

Project description:To investigate the effect of Mettl3 in the uterus, we generated mice with conditional ablation of Mettl3 in progesterone receptor (PR)–positive cells (PgrCre Mettl3 fl/fl). And the uterus of Mettl3 cKO and control mice on GD4 were obtained for RNA-seq analysis.

2023-09-07 | GSE208096 | GEO

The impact of progesterone levels and timing of progesterone exposure on human endometrial receptivity

Project description:Different progesterone levels and timing of exposure results in different endometrial gene expression and implantation potential. Sufficient progesterone level is important to induce endometrial receptivity and endometrial expressed the most receptive stage after exposure to progesterone for 7 days based on decidualisation marker expression.

2020-03-12 | GSE146777 | GEO

METTL3-dependent m<sup>6</sup>A methylation facilitates uterine receptivity and female fertility via balancing estrogen and progesterone signaling.

Project description:Infertility is a worldwide reproductive health problem and there are still many unknown etiologies of infertility. In recent years, increasing evidence emerged and confirmed that epigenetic regulation played a leading role in reproduction. However, the function of m6A modification in infertility remains unknown. Here we report that METTL3-dependent m6A methylation plays an essential role in female fertility via balancing the estrogen and progesterone signaling. Analysis of GEO datasets reveal a significant downregulation of METTL3 expression in the uterus of infertile women with endometriosis or recurrent implantation failure. Conditional deletion of Mettl3 in female reproductive tract by using a Pgr-Cre driver results in infertility due to compromised uterine endometrium receptivity and decidualization. m6A-seq analysis of the uterus identifies the 3'UTR of several estrogen-responsive genes with METTL3-dependent m6A modification, like Elf3 and Celsr2, whose mRNAs become more stable upon Mettl3 depletion. However, the decreased expression levels of PR and its target genes, including Myc, in the endometrium of Mettl3 cKO mice indicate a deficiency in progesterone responsiveness. In vitro, Myc overexpression could partially compensate for uterine decidualization failure caused by Mettl3 deficiency. Collectively, this study reveals the role of METTL3-dependent m6A modification in female fertility and provides insight into the pathology of infertility and pregnancy management.

| S-EPMC10239469 | biostudies-literature

Single cell RNA sequencing analysis of Mig-6 mutant mouse reveals progesterone susceptibility genes for uterine receptivity

Project description:The majority of pregnancy losses result from implantation failure. Successful embryo implantation involves a delicate interaction between the receptive uterus and an implantation-competent blastocyst. Understanding the mechanisms regulating the endometrial receptivity during preimplantation are essential for improving pregnancy outcomes. Mitogen-inducible gene 6 (MIG-6) is a key mediator of progesterone signaling in the endometrium.MIG-6 loss results in implantation failure due to non-receptive endometrium. We applied single cell RNA sequencing to determine the composition of different cell types and functions within non-receptive endometrium from uterine specific Mig-6 knock-out (Pgrcre/+Mig-6f/f; Mig-6d/d) mice. Mig-6d/d mice revealed altered gene expression in the epithelial and stromal cells. We identified key gene expression changes in the non-receptive endometrium of Mig-6d/d mice, providing valuable insights into the role of progesterone signaling in implantation.

2025-03-21 | GSE290275 | 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 impact of progesterone levels and timing of progesterone exposure on human endometrial receptivity

Project description:The impact of progesterone levels and timing of progesterone exposure on human endometrial receptivity

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Progesterone receptor in uterine glands is required for pregnancy establishment in mice

Project description:By utilizing Prss29-Cre, Pgr was conditionally deleted to identify the definitive roles of progesterone signaling in the uterine glands during pregnancy. This study provides new insights, demonstrating that PGR-P4 signaling in the glandular epithelium is required for uterine receptivity by regulating LIF on gestation day 4. Furthermore, we have shown that PGR signaling in glands is dispensable post-implantation.

2025-03-26 | GSE292591 | GEO

Decreased epithelial Progesterone Receptor A at the window of receptivity is required for preparation of the endometrium for embryo attachment

Project description:The progesterone receptor A (PGRA) isoform is the dominantly expressed isoform within the mouse uterus and is indispensable for uterine function and fertility in the murine reproductive tract. During early pregnancy, the PGRA isoform is spatiotemporally expressed in the uterine epithelium. At days 2-3 of pregnancy, PGRA is upregulated within the epithelium and then decreases before day 4, the day of embryo implantation. This decrease of PGRA has been recognized as a marker to initiate the time in which the uterus is receptive to the embryo, yet this has never been functionally tested. We hypothesized the decrease of PGRA at the window of receptivity is required for successful embryo implantation. In order to test this hypothesis, we generated a PGRA conditional expression allele initiated by Cre recombinase present in the uterine epithelial compartment. The PGRA expressing mice exhibited infertility with the inability to undergo embryo implantation or decidualization. RNA microarray and ChIP-Seq analyses were utilized to identify the differentially regulated pathways controlled by PGRA at the time of implantation.

2019-08-29 | GSE86303 | GEO

Single cell RNA sequencing analysis of Mig-6 mutant mouse reveals progesterone susceptibility genes for uterine receptivity

Project description:Single cell RNA sequencing analysis of Mig-6 mutant mouse reveals progesterone susceptibility genes for uterine receptivity

| PRJNA1227122 | ENA

Concentrations of progesterone prior to luteolysis modulates the uterine luminal transcriptome in the subsequent cycle in cattle

Project description:Sex-steroids concentrations throughout the estrous cycle modulate endometrial function and fertility in cattle. The objective of this study was to compare the post-estrus endometrial transcriptome of cows that were exposed to contrasting pre-estrus concentrations of progesterone before they displayed estrus and ovulated spontaneously. We hypothesized that greater pre-estrus concentration of progesterone alters post-estrus endometrial function even after the display of estrus and spontaneous ovulation.

2022-04-13 | GSE200361 | GEO

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