Organoids to model the endometrium: implantation and beyond

Rawlings, Thomas M; Makwana, Komal; Tryfonos, Maria; Lucas, Emma S.

doi:10.1530/raf-21-0023

Cited by 26 publications

(15 citation statements)

References 136 publications

(224 reference statements)

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“…Studies in cultured stromal cells are one key model, as they are amenable to mechanistic studies; however, in vitro models in which to study epithelial cells have proven challenging. Recently, however, innovative organoid culture systems have been developed that provide a platform to study processes intrinsic to endometrial epithelial cells [ 23 , 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

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%

Progesterone Signaling in Endometrial Epithelial Organoids

Hewitt

Wang

et al. 2022

Cells

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“…There are many technical and ethical challenges to overcome in defining the intricacies of human embryo implantation, and there are still many aspects that are not fully understood. Much of our knowledge of embryo implantation has stemmed from animal studies and in vitro two-dimensional (2D) monolayer culture systems, neither of which accurately represent the in vivo endometrial or embryo physiology, or environment [ 48 , 171 ]. 3D investigation of the human endometrium and embryo implantation is an important avenue for future research [ 48 , 51 , 52 ].…”

Section: Avenues For Future Researchmentioning

confidence: 99%

“…3D investigation of the human endometrium and embryo implantation is an important avenue for future research [ 48 , 51 , 52 ]. The advent of ‘organoids’ has led to huge advances in in vitro 3D modelling techniques [ 171 , 172 , 173 ]. Endometrial organoids arise from single or small clusters of cells and resemble endometrial tissue ex vivo [ 174 ].…”

Section: Avenues For Future Researchmentioning

confidence: 99%

The Role of Endometrial Stem/Progenitor Cells in Recurrent Reproductive Failure

Al-Lamee

Hill

Turner

et al. 2022

JPM

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Recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL), collectively referred to as recurrent reproductive failure (RRF), are both challenging conditions with many unanswered questions relating to causes and management options. Both conditions are proposed to be related to an aberrant endometrial microenvironment, with different proposed aetiologies related to a restrictive or permissive endometrium for an invading embryo. The impressive regenerative capacity of the human endometrium has been well-established and has led to the isolation and characterisation of several subtypes of endometrial stem/progenitor cells (eSPCs). eSPCs are known to be involved in the pathogenesis of endometrium-related disorders (such as endometriosis) and have been proposed to be implicated in the pathogenesis of RRF. This review appraises the current knowledge of eSPCs, and their involvement in RRF, highlighting the considerable unknown aspects in this field, and providing avenues for future research to facilitate much-needed advances in the diagnosis and management of millions of women suffering with RRF.

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“…Previously, cultures of 3D uterine glands explants and stromal cells had limited viability surviving only for four days with the resemblance of spheroids beginning to form (Stadler et al, 2009). Endometrium organoids may be useful for investigating endometriosis and endometrial cancers (Turco et al, 2017), as well as studies regarding implantation (Rawlings et al, 2021). Research regarding human physiology and the function of the endometrium is difficult due to variability between individuals; however, co-culturing endometrium organoids on three-dimensional scaffolds may allow investigation into implantation studies (Cindrova-Davies et al, 2021).…”

Section: Uterusmentioning

confidence: 99%

A Multi-Tissue Comparison and Molecular Characterization of Canine Organoids

Zdyrski

Gabriel

Ospina

et al. 2022

Preprint

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Organoids are 3-dimensional (3D) stem cell-derived cell culture lines that offer a variety of technical advantages compared to traditional 2-dimensional (2D) cell cultures. Although murine models have proved useful in biomedical research, rodent models often fail to adequately mimic human physiology and disease progression, resulting in poor preclinical prediction of therapeutic drug efficacy and toxicity. With the advent of organoid technology, many of these challenges can be overcome. Previously, the use of canine organoids in drug testing and disease modeling was limited to organoids originating from the intestine, liver, kidney, and urinary bladder. Here, we report the cultivation, maintenance, and molecular characterization of three novel adult-stem cell-derived canine organoid cell lines, including the endometrium, lung, and pancreas, in addition to previously reported kidney, bladder, and liver organoids from two genetically related canines. Six tissues and organoid lines from each donor were characterized using bulk RNASeq, allowing for a unique, multi-organ comparison between these two individuals and identification of specific cell types such as glandular epithelial cells in endometrial organoids.

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Organoids to model the endometrium: implantation and beyond

Cited by 26 publications

References 136 publications

Progesterone Signaling in Endometrial Epithelial Organoids

Progesterone Signaling in Endometrial Epithelial Organoids

The Role of Endometrial Stem/Progenitor Cells in Recurrent Reproductive Failure

A Multi-Tissue Comparison and Molecular Characterization of Canine Organoids

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