Organoid systems to study the human female reproductive tract and pregnancy

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Abstract

Both the proper functioning of the female reproductive tract (FRT) and normal placental development are essential for women’s health, wellbeing, and pregnancy outcome. The study of the FRT in humans has been challenging due to limitations in the in vitro and in vivo tools available. Recent developments in 3D organoid technology that model the different regions of the FRT include organoids of the ovaries, fallopian tubes, endometrium and cervix, as well as placental trophoblast. These models are opening up new avenues to investigate the normal biology and pathology of the FRT. In this review, we discuss the advances, potential, and limitations of organoid cultures of the human FRT.

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Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche.

Toshiro Sato, Robert G J Vries, Hugo J. Snippert … (2009)

The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. We have recently demonstrated the presence of about six cycling Lgr5(+) stem cells at the bottoms of small-intestinal crypts. Here we describe the establishment of long-term culture conditions under which single crypts undergo multiple crypt fission events, while simultanously generating villus-like epithelial domains in which all differentiated cell types are present. Single sorted Lgr5(+) stem cells can also initiate these cryptvillus organoids. Tracing experiments indicate that the Lgr5(+) stem-cell hierarchy is maintained in organoids. We conclude that intestinal cryptvillus units are self-organizing structures, which can be built from a single stem cell in the absence of a non-epithelial cellular niche.

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In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus

Raimunda Azevedo, Jorge R. de Sousa, Marialva Araujo … (2018)

Zika virus (ZIKV) has recently caused a pandemic disease, and many cases of ZIKV infection in pregnant women resulted in abortion, stillbirth, deaths and congenital defects including microcephaly, which now has been proposed as ZIKV congenital syndrome. This study aimed to investigate the in situ immune response profile and mechanisms of neuronal cell damage in fatal Zika microcephaly cases. Brain tissue samples were collected from 15 cases, including 10 microcephalic ZIKV-positive neonates with fatal outcome and five neonatal control flavivirus-negative neonates that died due to other causes, but with preserved central nervous system (CNS) architecture. In microcephaly cases, the histopathological features of the tissue samples were characterized in three CNS areas (meninges, perivascular space, and parenchyma). The changes found were mainly calcification, necrosis, neuronophagy, gliosis, microglial nodules, and inflammatory infiltration of mononuclear cells. The in situ immune response against ZIKV in the CNS of newborns is complex. Despite the predominant expression of Th2 cytokines, other cytokines such as Th1, Th17, Treg, Th9, and Th22 are involved to a lesser extent, but are still likely to participate in the immunopathogenic mechanisms of neural disease in fatal cases of microcephaly caused by ZIKV.

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Epidemiology of ovarian cancer: a review

Brett M. Reid, Jennifer B. Permuth, Thomas Sellers (2017)

Ovarian cancer (OC) is the seventh most commonly diagnosed cancer among women in the world and the tenth most common in China. Epithelial OC is the most predominant pathologic subtype, with five major histotypes that differ in origination, pathogenesis, molecular alterations, risk factors, and prognosis. Genetic susceptibility is manifested by rare inherited mutations with high to moderate penetrance. Genome-wide association studies have additionally identified 29 common susceptibility alleles for OC, including 14 subtype-specific alleles. Several reproductive and hormonal factors may lower risk, including parity, oral contraceptive use, and lactation, while others such as older age at menopause and hormone replacement therapy confer increased risks. These associations differ by histotype, especially for mucinous OC, likely reflecting differences in etiology. Endometrioid and clear cell OC share a similar, unique pattern of associations with increased risks among women with endometriosis and decreased risks associated with tubal ligation. OC risks associated with other gynecological conditions and procedures, such as hysterectomy, pelvic inflammatory disease, and polycystic ovarian syndrome, are less clear. Other possible risk factors include environmental and lifestyle factors such as asbestos and talc powder exposures, and cigarette smoking. The epidemiology provides clues on etiology, primary prevention, early detection, and possibly even therapeutic strategies.

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Author and article information

Contributors

Margherita Y. Turco:

ORCID: http://orcid.org/0000-0002-3380-7375

myt25@cam.ac.uk

Journal

Journal ID (nlm-ta): Cell Death Differ

Journal ID (iso-abbrev): Cell Death Differ

Title: Cell Death and Differentiation

Publisher: Nature Publishing Group UK (London )

ISSN (Print): 1350-9047

ISSN (Electronic): 1476-5403

Publication date (Electronic): 3 June 2020

Publication date PMC-release: 3 June 2020

Publication date (Print): January 2021

Volume: 28

Issue: 1

Pages: 35-51

Affiliations

[1 ]GRID grid.5335.0, ISNI 0000000121885934, Department of Pathology, , University of Cambridge, ; Tennis Court Road, Cambridge, CB2 1QP UK

[2 ]Centre for Trophoblast Research, Downing Street, Cambridge, CB2 3EG UK

Author information

Margherita Y. Turco http://orcid.org/0000-0002-3380-7375

Article

Publisher ID: 565

DOI: 10.1038/s41418-020-0565-5

PMC ID: 7852529

PubMed ID: 32494027

SO-VID: 70de516f-bd30-4f13-a325-f83f28c30ce7

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 4 February 2020

Date revision received : 24 April 2020

Date accepted : 15 May 2020

Funding

Funded by: FundRef https://doi.org/10.13039/501100000288, Royal Society;

Award ID: DH160216

Award Recipient : Margherita Y. Turco

Funded by: FundRef https://doi.org/10.13039/501100004815, Isaac Newton Trust;

Award ID: G100391

Award Recipient : Margherita Y. Turco

Funded by: FundRef https://doi.org/10.13039/100010663, EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council);

Award ID: 853546

Award Recipient : Margherita Y. Turco

Funded by: Centre for Trophoblast Research L'Oreal Women in Science Fellowship

Funded by: FundRef https://doi.org/10.13039/501100002383, King Saud University (KSU);

Award ID: KSU1520

Award Recipient : Lama Alzamil

Funded by: FundRef https://doi.org/10.13039/100004440, Wellcome Trust (Wellcome);

Award ID: UNS13724

Award Recipient : Konstantina Nikolakopoulou

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ScienceOpen disciplines: Cell biology

Keywords: cell biology,physiology,diseases

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ScienceOpen disciplines: Cell biology

Keywords: cell biology, physiology, diseases

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Organoid systems to study the human female reproductive tract and pregnancy

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Evolutionary Cell Biology

Most cited references 135

Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche.

In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus

Epidemiology of ovarian cancer: a review

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