Reproduction (Cambridge, England)2020; 160(6); 819-831; doi: 10.1530/REP-20-0266

Hormone-responsive organoids from domestic mare and endangered Przewalski’s horse endometrium.

Abstract: The endometrium, the inner uterine lining, is composed of cell layers that come in direct contact with an embryo during early pregnancy and later with the fetal placenta. The endometrium is responsible for signals associated with normal reproductive cyclicity as well as maintenance of pregnancy. In the mare, functionally competent in vitro models of the endometrium have not been successful. Furthermore, the ability to study various reproductive processes in vitro may allow critical evaluation of signaling pathways involved in the reproductive diseases of animals that cannot be handled frequently, such as various wildlife species. Here we report the establishment of organoids, 3D structures, derived from fresh and frozen-thawed equine endometrium (Equus ferus caballus and E. f. przewalskii). Although organoids from domestic mares responded to exogenous hormonal stimuli, organoids from Przewalski's horse failed to respond to exogenous hormones. The present study represents a 'first' for any large animal model or endangered species. These physiologically functional organoids may facilitate improved understanding of normal reproductive mechanisms, uterine pathologies, and signaling mechanisms between the conceptus and endometrium and may lead to the development of novel bioassays for drug discovery.
Publication Date: 2020-10-29 PubMed ID: 33112764DOI: 10.1530/REP-20-0266Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research explores the creation of 3D cell structures, called organoids, from the uterine lining of domestic and endangered horses. It found that these organoids responded differently to hormonal stimuli, a discovery that could enhance our understanding of reproductive mechanisms and help in the development of new drug tests.

Context and Objective of the Study

  • The endometrium is the inner lining of the uterus. It comes into direct contact with an embryo during early stages of pregnancy and with the fetal placenta later on. It is responsible for signals related to normal reproductive cycles and pregnancy maintenance.
  • Previous attempts to create functional models of the horse endometrium in vitro have been unsuccessful.
  • The goal of this research was to establish organoids, which are three-dimensional structures, from the endometrium of both a domestic horse breed (Equus ferus caballus) and an endangered breed (E. f. przewalskii).

Main Findings

  • The researchers were able to create organoids from both fresh and frozen-thawed equine endometrium cells.
  • These organoids from domestic mares responded to externally introduced hormonal stimuli. However, the ones derived from the endangered Przewalski’s horse did not show a response to these hormones.

Implications and Future Directions

  • This study represents a new achievement for research involving large animal models or endangered species.
  • These functionally active organoids may contribute to a better understanding of normal reproductive mechanisms, uterine diseases, and the signaling pathways between a fetus and the endometrium.
  • In the future, these organoids could also lead to the development of new bioassays for drug discovery. By testing drugs on these 3D cell structures, researchers may be able to predict how the drugs would interact with live tissues and possibly minimize any harmful impact during actual trials.

Cite This Article

APA
Thompson RE, Johnson AK, Dini P, Turco MY, Prado TM, Premanandan C, Burton GJ, Ball BA, Whitlock BK, Pukazhenthi BS. (2020). Hormone-responsive organoids from domestic mare and endangered Przewalski’s horse endometrium. Reproduction, 160(6), 819-831. https://doi.org/10.1530/REP-20-0266

Publication

ISSN: 1741-7899
NlmUniqueID: 100966036
Country: England
Language: English
Volume: 160
Issue: 6
Pages: 819-831

Researcher Affiliations

Thompson, Riley E
  • Department of Large Animal Clinical Sciences, University of Tennessee, Knoxville, Tennessee, USA.
  • Center for Species Survival, Smithsonian Conservation Biology Institute, Front Royal, Virginia, USA.
Johnson, Aime K
  • Department of Clinical Sciences, Auburn University, Auburn, Alabama, USA.
Dini, Pouya
  • Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
Turco, Margherita Y
  • Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.
Prado, Tulio M
  • Department of Large Animal Clinical Sciences, University of Tennessee, Knoxville, Tennessee, USA.
Premanandan, Christopher
  • Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA.
Burton, Graham J
  • Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.
Ball, Barry A
  • Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
Whitlock, Brian K
  • Department of Large Animal Clinical Sciences, University of Tennessee, Knoxville, Tennessee, USA.
Pukazhenthi, Budhan S
  • Center for Species Survival, Smithsonian Conservation Biology Institute, Front Royal, Virginia, USA.

MeSH Terms

  • Animals
  • Animals, Wild
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Endometrium / drug effects
  • Endometrium / metabolism
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism
  • Female
  • Gene Expression Regulation / drug effects
  • Hormones / pharmacology
  • Horses
  • Organoids / drug effects
  • Organoids / metabolism
  • Receptors, Progesterone / genetics
  • Receptors, Progesterone / metabolism

Citations

This article has been cited 7 times.
  1. De Vriendt S, Casares CM, Rocha S, Vankelecom H. Matrix scaffolds for endometrium-derived organoid models.. Front Endocrinol (Lausanne) 2023;14:1240064.
    doi: 10.3389/fendo.2023.1240064pubmed: 37635971google scholar: lookup
  2. Penning LC, van den Boom R. Companion animal organoid technology to advance veterinary regenerative medicine.. Front Vet Sci 2023;10:1032835.
    doi: 10.3389/fvets.2023.1032835pubmed: 37008367google scholar: lookup
  3. Thompson RE, Meyers MA, Veeramachaneni DNR, Pukazhenthi BS, Hollinshead FK. Equine Oviductal Organoid Generation and Cryopreservation.. Methods Protoc 2022 Jun 15;5(3).
    doi: 10.3390/mps5030051pubmed: 35736552google scholar: lookup
  4. Kawasaki M, Goyama T, Tachibana Y, Nagao I, Ambrosini YM. Farm and Companion Animal Organoid Models in Translational Research: A Powerful Tool to Bridge the Gap Between Mice and Humans.. Front Med Technol 2022;4:895379.
    doi: 10.3389/fmedt.2022.895379pubmed: 35647577google scholar: lookup
  5. Thompson RE, Bouma GJ, Hollinshead FK. The Roles of Extracellular Vesicles and Organoid Models in Female Reproductive Physiology.. Int J Mol Sci 2022 Mar 16;23(6).
    doi: 10.3390/ijms23063186pubmed: 35328607google scholar: lookup
  6. Sang Y, Miller LC, Nelli RK, Gimu00e9nez-Lirola LG. Harness Organoid Models for Virological Studies in Animals: A Cross-Species Perspective.. Front Microbiol 2021;12:725074.
    doi: 10.3389/fmicb.2021.725074pubmed: 34603253google scholar: lookup
  7. Swegen A. Maternal recognition of pregnancy in the mare: does it exist and why do we care?. Reproduction 2021 May 5;161(6):R139-R155.
    doi: 10.1530/REP-20-0437pubmed: 33957605google scholar: lookup