The role of epithelial progesterone receptor isoforms in embryo implantation

Li, Rong; Wang, Xiaoqiu; Huang, Zhenyao; Balaji, Jayani; Kim, Tae Hoon; Wang, Tianyuan; Zhou, Lecong; Deleon, Ashley; Cook, Molly E.; Marbrey, Margeaux W.; Wu, San‐Pin; Jeong, Jae Wook; Arora, Ritu; DeMayo, Francesco J.

doi:10.1016/j.isci.2021.103487

Cited by 22 publications

(15 citation statements)

References 89 publications

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“…These observations emphasize the key role of epithelial PGR in the establishment of receptivity. Conversely, mouse models with persistent epithelial PGR-A or PGR-B overexpression are unable to establish a receptive uterus [ 12 , 13 ], which illustrates the importance of appropriate dynamics of epithelial cell PGR levels for fertility. In women, progesterone is important not just for fertility but also for general endometrial health.…”

Section: Introductionmentioning

confidence: 99%

“…Using ChIPseq, the sites of receptor/chromatin interaction, or cistrome, can be determined in particular cells and tissues. The PGR cistrome of mouse uterine tissue [ 13 , 17 ] and human endometrial biopsies [ 18 ] have been described and indicate that PGR binds near genes, as well as in distal enhancers. These distal sites are called enhancers because they interact with numerous transcription factors and histones with activating modifications to enhance gene transcription.…”

Section: Introductionmentioning

confidence: 99%

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Progesterone Signaling in Endometrial Epithelial Organoids

Hewitt

Wang

et al. 2022

Cells

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For pregnancy to be established, uterine cells respond to the ovarian hormones, estrogen, and progesterone, via their nuclear receptors, the estrogen receptor (ESR1) and progesterone receptor (PGR). ESR1 and PGR regulate genes by binding chromatin at genes and at distal enhancer regions, which interact via dynamic 3-dimensional chromatin structures. Endometrial epithelial cells are the initial site of embryo attachment and invasion, and thus understanding the processes that yield their receptive state is important. Here, we cultured and treated organoids derived from human epithelial cells, isolated from endometrial biopsies, with estrogen and progesterone and evaluated their transcriptional profiles, their PGR cistrome, and their chromatin conformation. Progesterone attenuated estrogen-dependent gene responses but otherwise minimally impacted the organoid transcriptome. PGR ChIPseq peaks were co-localized with previously described organoid ESR1 peaks, and most PGR and ESR1 peaks were in B (inactive) compartment regions of chromatin. Significantly more ESR1 peaks were assigned to estrogen-regulated genes by considering chromatin loops identified using HiC than were identified using ESR1 peak location relative to closest genes. Overall, the organoids model allowed a definition of the chromatin regulatory components governing hormone responsiveness.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Progesterone Signaling in Endometrial Epithelial Organoids

Hewitt

Wang

et al. 2022

Cells

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“…The PI3 kinase (PI3K) signaling pathway, likely acting through serum/glucocorticoid regulated kinase 1 (SGK1), is an important regulator of FOXO1 phosphorylation and function in mice and in a human endometrial cell line [10].…”

Section: Mechanisms Governing Human Endometrial Receptivitymentioning

confidence: 99%

Evaluation of endometrial receptivity and implantation failure

Bui

Timmons

Young

2022

Current Opinion in Obstetrics &Amp; Gynecology

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Purpose of reviewTo succinctly review the basic mechanisms of implantation and luteal phase endometrial differentiation, the etiologies of impaired endometrial function and receptivity, and the current methods that exist to evaluate and treat impaired endometrial receptivity. Recent findingsHuman embryo implantation requires bidirectional communication between blastocyst and a receptive endometrium. Etiologies of impaired endometrial receptivity are varied. Some of these include delayed endometrial maturation, structural abnormalities, inflammation, and progesterone resistance. Current methods to evaluate endometrial receptivity include ultrasonography, hysteroscopy, and endometrial biopsy. Treatments are limited, but include operative hysteroscopy, treatment of endometriosis, and personalized timing of embryo transfer.

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“…One of the leading causes of recurring early pregnancy loss is embryo implantation failure and consequent embryonic death [ 1 ]. Hormonal treatment such as progesterone is frequently used to stimulate and support pregnancy, with maternal tissues being its primary target [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Progesterone Receptor Modulates Extraembryonic Mesoderm and Cardiac Progenitor Specification during Mouse Gastrulation

Drozd

Mariani

Guo

et al. 2022

IJMS

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Progesterone treatment is commonly employed to promote and support pregnancy. While maternal tissues are the main progesterone targets in humans and mice, its receptor (PGR) is expressed in the murine embryo, questioning its function during embryonic development. Progesterone has been previously associated with murine blastocyst development. Whether it contributes to lineage specification is largely unknown. Gastrulation initiates lineage specification and generation of the progenitors contributing to all organs. Cells passing through the primitive streak (PS) will give rise to the mesoderm and endoderm. Cells emerging posteriorly will form the extraembryonic mesodermal tissues supporting embryonic growth. Cells arising anteriorly will contribute to the embryonic heart in two sets of distinct progenitors, first (FHF) and second heart field (SHF). We found that PGR is expressed in a posterior–anterior gradient in the PS of gastrulating embryos. We established in vitro differentiation systems inducing posterior (extraembryonic) and anterior (cardiac) mesoderm to unravel PGR function. We discovered that PGR specifically modulates extraembryonic and cardiac mesoderm. Overexpression experiments revealed that PGR safeguards cardiac differentiation, blocking premature SHF progenitor specification and sustaining the FHF progenitor pool. This role of PGR in heart development indicates that progesterone administration should be closely monitored in potential early-pregnancy patients undergoing infertility treatment.

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The role of epithelial progesterone receptor isoforms in embryo implantation

Cited by 22 publications

References 89 publications

Progesterone Signaling in Endometrial Epithelial Organoids

Progesterone Signaling in Endometrial Epithelial Organoids

Evaluation of endometrial receptivity and implantation failure

Progesterone Receptor Modulates Extraembryonic Mesoderm and Cardiac Progenitor Specification during Mouse Gastrulation

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