Uterine Luminal Epithelium as the Transient Gateway for Embryo Implantation

Ye, Xiaoqin

doi:10.1016/j.tem.2019.11.008

Cited by 72 publications

(39 citation statements)

References 103 publications

(188 reference statements)

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“…We were also interested in genes differentially expressed in LE. Blastocyst attachment to the uterine LE occurs at midnight of gestational day 4 and a firm connection between blastocyst attachment to the uterine LE is established on the morning of gestational day 5 [ 27 ]. We identified 391 differentially expressed genes in LE, of which 132 genes were upregulated and 259 genes were downregulated in IS compared to IIS.…”

Section: Discussionmentioning

confidence: 99%

Cell–Cell Communication at the Embryo Implantation Site of Mouse Uterus Revealed by Single-Cell Analysis

Yang

Liu

2021

IJMS

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As a crucial step for human reproduction, embryo implantation is a low-efficiency process. Despite rapid advances in recent years, the molecular mechanism underlying embryo implantation remains poorly understood. Here, we used the mouse as an animal model and generated a single-cell transcriptomic atlas of embryo implantation sites. By analyzing inter-implantation sites of the uterus as control, we were able to identify global gene expression changes associated with embryo implantation in each cell type. Additionally, we predicted signaling interactions between uterine luminal epithelial cells and mural trophectoderm of blastocysts, which represent the key mechanism of embryo implantation. We also predicted signaling interactions between uterine epithelial-stromal crosstalk at implantation sites, which are crucial for post-implantation development. Our data provide a valuable resource for deciphering the molecular mechanism underlying embryo implantation.

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Section: Discussionmentioning

confidence: 99%

Cell–Cell Communication at the Embryo Implantation Site of Mouse Uterus Revealed by Single-Cell Analysis

Yang

Liu

2021

IJMS

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“…The endometrium becomes functional, undergoing cyclical regression and regeneration, when the reproductive hormones estrogen and progesterone are secreted by the ovaries. The LE regulates embryo attachment for implantation, and GE regulates embryo survival and growth, stromal cell decidualization and placental development (Wang et al, 2013;Spencer et al, 2019;Ye, 2020). To date, there are no definitive stem cell markers for the mouse endometrium.…”

Section: Mouse Endometrial Epithelial Stem/progenitor Cellsmentioning

confidence: 99%

The Elusive Endometrial Epithelial Stem/Progenitor Cells

Cousins

Pandoy

Jin

et al. 2021

Front. Cell Dev. Biol.

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The human endometrium undergoes approximately 450 cycles of proliferation, differentiation, shedding and regeneration over a woman’s reproductive lifetime. The regenerative capacity of the endometrium is attributed to stem/progenitor cells residing in the basalis layer of the tissue. Mesenchymal stem cells have been extensively studied in the endometrium, whereas endometrial epithelial stem/progenitor cells have remained more elusive. This review details the discovery of human and mouse endometrial epithelial stem/progenitor cells. It highlights recent significant developments identifying putative markers of these epithelial stem/progenitor cells that reveal their in vivo identity, location in both human and mouse endometrium, raising common but also different viewpoints. The review also outlines the techniques used to identify epithelial stem/progenitor cells, specifically in vitro functional assays and in vivo lineage tracing. We will also discuss their known interactions and hierarchy and known roles in endometrial dynamics across the menstrual or estrous cycle including re-epithelialization at menses and regeneration of the tissue during the proliferative phase. We also detail their potential role in endometrial proliferative disorders such as endometriosis.

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“…uterus | gland | FOXA2 | pregnancy | placenta I n mice, the initiation of embryo attachment and implantation, occurring late on gestational day (GD) 4, is followed by extensive proliferation of stromal cells surrounding the nidating blastocyst on the morning of GD 5 (1)(2)(3). Between GDs 5 and 6, stromal cells, adjacent to the implanted blastocyst in the antimesometrial (AM) region of the uterus, cease proliferating and undergo differentiation into decidual cells, forming the primary decidual zone (PDZ), an area that is avascular and epithelioid in nature (4).…”

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confidence: 99%

Sexually dimorphic effects of forkhead box a2 (FOXA2) and uterine glands on decidualization and fetoplacental development

Dhakal

Kelleher

Behura

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Glands of the uterus are essential for pregnancy establishment. Forkhead box A2 (FOXA2) is expressed specifically in the glands of the uterus and a critical regulator of glandular epithelium (GE) differentiation, development, and function. Mice with a conditional deletion of FOXA2 in the adult uterus, created using the lactotransferrin iCre (Ltf-iCre) model, have a morphologically normal uterus with glands, but lack FOXA2-dependent GE-expressed genes, such as leukemia inhibitory factor (LIF). Adult FOXA2 conditional knockout (cKO; LtfiCre/+Foxa2f/f) mice are infertile due to defective embryo implantation arising from a lack of LIF, a critical implantation factor of uterine gland origin. However, intraperitoneal injections of LIF can initiate embryo implantation in the uterus of adult FOXA2 cKO mice with pregnancies maintained to term. Here, we tested the hypothesis that FOXA2-regulated genes in the uterine glands impact development of the decidua, placenta, and fetus. On gestational day 8.5, the antimesometrial and mesometrial decidua transcriptome was noticeably altered in LIF-replaced FOXA2 cKO mice. Viable fetuses were reduced in FOXA2 cKO mice on gestational days 12.5 and 17.5. Sex-dependent differences in fetal weight, placenta histoarchitecture, and the placenta and metrial gland transcriptome were observed between control and FOXA2 cKO mice. The transcriptome of the placenta with a female fetus was considerably more altered than the placenta with a male fetus in FOXA2 cKO dams. These studies reveal previously unrecognized sexually dimorphic effects of FOXA2 and uterine glands on fetoplacental development with potential impacts on offspring health into adulthood.

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Uterine Luminal Epithelium as the Transient Gateway for Embryo Implantation

Cited by 72 publications

References 103 publications

Cell–Cell Communication at the Embryo Implantation Site of Mouse Uterus Revealed by Single-Cell Analysis

Cell–Cell Communication at the Embryo Implantation Site of Mouse Uterus Revealed by Single-Cell Analysis

The Elusive Endometrial Epithelial Stem/Progenitor Cells

Sexually dimorphic effects of forkhead box a2 (FOXA2) and uterine glands on decidualization and fetoplacental development

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