Menstrual flow as a non-invasive source of endometrial organoids

Cindrová‐Davies, Tereza; Zhao, Xiaohui; Elder, Kay; Jones, Carolyn J.P.; Moffett, Ashley; Burton, Graham J.; Turco, Margherita Y.

doi:10.1038/s42003-021-02194-y

Cited by 52 publications

(41 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our method of generating MFO involves selecting EpCAM + gland fragments by magnetic beading. A recent work [22] that was completed at the same time as ours confirms our initial observations that MFO can also be derived from unbeaded endometrial epithelial fragments from a small fraction of cells obtained from previous studies [9]. On the other hand, methods for standard EMO (and therefore EMO-H) generate EMO from fragments of unbeaded endometrial tissue that are separated by filtration and therefore may contain stromal tissue fragments or other cell types.…”

Section: Discussionsupporting

confidence: 88%

“…The individual gene expression profiles also clustered based on disease state for several gene sets. A number of GO gene sets as well as curated gene sets generated by us and others [22] showed the clustering of two control participants (23_20 and MR041B) compared to the other five participants. This included Epithelial Secretory Activity (Figure 7a) and Androgen Receptor Signalling and both the Regulation and Negative Regulation of Androgen Receptor Signalling (Figure 7b-d).…”

Section: Disease State Gene Expression Profilesmentioning

confidence: 88%

See 1 more Smart Citation

Comparison of Organoids from Menstrual Fluid and Hormone-Treated Endometrium: Novel Tools for Gynecological Research

Filby

Wyatt

Mortlock

et al. 2021

JPM

View full text Add to dashboard Cite

Endometrial organoids (EMO) are an important tool for gynecological research but have been limited by generation from (1) invasively acquired tissues and thus advanced disease states and (2) from women who are not taking hormones, thus excluding 50% of the female reproductive-aged population. We sought to overcome these limitations by generating organoids from (1) menstrual fluid (MF; MFO) using a method that enables the concurrent isolation of menstrual fluid supernatant, stromal cells, and leukocytes and (2) from biopsies and hysterectomy samples from women taking hormonal medication (EMO-H). MF was collected in a menstrual cup for 4–6 h on day 2 of menstruation. Biopsies and hysterectomies were obtained during laparoscopic surgery. Organoids were generated from all sample types, with MFO and EMO-H showing similar cell proliferation rates, proportion and localization of the endometrial basalis epithelial marker, Stage Specific Embryonic Antigen-1 (SSEA-1), and gene expression profiles. Organoids from different disease states showed the moderate clustering of epithelial secretory and androgen receptor signaling genes. Thus, MFO and EMO-H are novel organoids that share similar features to EMO but with the advantage of (1) MFO being obtained non-invasively and (2) EMO-H being obtained from 50% of the women who are not currently being studied through standard methods. Thus, MFO and EMO-H are likely to prove to be invaluable tools for gynecological research, enabling the population-wide assessment of endometrial health and personalized medicine.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Disease State Gene Expression Profilesmentioning

confidence: 88%

Comparison of Organoids from Menstrual Fluid and Hormone-Treated Endometrium: Novel Tools for Gynecological Research

Filby

Wyatt

Mortlock

et al. 2021

JPM

View full text Add to dashboard Cite

show abstract

“…We and others have established a three-dimensional in vitro organoid culture model of human endometrial epithelium 10 , 11 . These organoids are generated from dissociated endometrial tissue and menstrual fluid samples 12 ; they retain the morphology, function and gene signature of the tissue in vivo and respond functionally to ovarian hormones with differentiation into ciliated and secretory cells. They are therefore powerful platforms to investigate endometrial disorders and study mechanisms regulating endometrial differentiation in humans.…”

Section: Mainmentioning

confidence: 99%

Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro

et al. 2021

Self Cite

View full text Add to dashboard Cite

The endometrium, the mucosal lining of the uterus, undergoes dynamic changes throughout the menstrual cycle in response to ovarian hormones. We have generated dense single-cell and spatial reference maps of the human uterus and three-dimensional endometrial organoid cultures. We dissect the signaling pathways that determine cell fate of the epithelial lineages in the lumenal and glandular microenvironments. Our benchmark of the endometrial organoids reveals the pathways and cell states regulating differentiation of the secretory and ciliated lineages both in vivo and in vitro. In vitro downregulation of WNT or NOTCH pathways increases the differentiation efficiency along the secretory and ciliated lineages, respectively. We utilize our cellular maps to deconvolute bulk data from endometrial cancers and endometriotic lesions, illuminating the cell types dominating in each of these disorders. These mechanistic insights provide a platform for future development of treatments for common conditions including endometriosis and endometrial carcinoma.

show abstract

“…For example, equine endometrial organoids responded to oxytocin hormone treatment with changes in PTGS2 , PGES , and OXTR , which are genes associated with the prostaglandin synthesis cascade [ 36 ]. Cleverly, one group recently reported the successful generation of endometrial organoids from menstrual secretions in women, which was determined by confirming that endometrial organoids derived from biopsies and menstrual secretions display the same transcriptome signature, efficiency, proliferation rate, and response to exogenous steroid hormones, and precludes the need for tissue biopsies [ 37 ].…”

Section: In Vitro Models Used To Study Reproductive Physiologymentioning

confidence: 99%

The Roles of Extracellular Vesicles and Organoid Models in Female Reproductive Physiology

Thompson

Bouma

Hollinshead

2022

IJMS

View full text Add to dashboard Cite

Culture model systems that can recapitulate the anatomy and physiology of reproductive organs, such as three-dimensional (3D) organoid culture systems, limit the cost and welfare concerns associated with a research animal colony and provide alternative approaches to study specific processes in humans and animals. These 3D models facilitate a greater understanding of the physiological role of individual cell types and their interactions than can be accomplished with traditional monolayer culture systems. Furthermore, 3D culture systems allow for the examination of specific cellular, molecular, or hormonal interactions, without confounding factors that occur with in vivo models, and provide a powerful approach to study physiological and pathological reproductive conditions. The goal of this paper is to review and compare organoid culture systems to other in vitro cell culture models, currently used to study female reproductive physiology, with an emphasis on the role of extracellular vesicle interactions. The critical role of extracellular vesicles for intercellular communication in physiological processes, including reproduction, has been well documented, and an overview of the roles of extracellular vesicles in organoid systems will be provided. Finally, we will propose future directions for understanding the role of extracellular vesicles in normal and pathological conditions of reproductive organs, utilizing 3D organoid culture systems.

show abstract

Menstrual flow as a non-invasive source of endometrial organoids

Cited by 52 publications

References 40 publications

Comparison of Organoids from Menstrual Fluid and Hormone-Treated Endometrium: Novel Tools for Gynecological Research

Comparison of Organoids from Menstrual Fluid and Hormone-Treated Endometrium: Novel Tools for Gynecological Research

Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro

The Roles of Extracellular Vesicles and Organoid Models in Female Reproductive Physiology

Contact Info

Product

Resources

About