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Stem Cell-Based Trophoblast Models to Unravel the Genetic Causes of Human Miscarriages

Miscarriage affects approximately 15% of clinically recognized pregnancies, and 1–3% of couples experience pregnancy loss recurrently. Approximately 50–60% of miscarriages result from chromosomal abnormalities, whereas up to 60% of euploid recurrent abortions harbor variants in candidate genes. The...

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Autores principales: Nikitina, Tatiana V., Lebedev, Igor N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221414/
https://www.ncbi.nlm.nih.gov/pubmed/35741051
http://dx.doi.org/10.3390/cells11121923
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author Nikitina, Tatiana V.
Lebedev, Igor N.
author_facet Nikitina, Tatiana V.
Lebedev, Igor N.
author_sort Nikitina, Tatiana V.
collection PubMed
description Miscarriage affects approximately 15% of clinically recognized pregnancies, and 1–3% of couples experience pregnancy loss recurrently. Approximately 50–60% of miscarriages result from chromosomal abnormalities, whereas up to 60% of euploid recurrent abortions harbor variants in candidate genes. The growing number of detected genetic variants requires an investigation into their role in adverse pregnancy outcomes. Since placental defects are the main cause of first-trimester miscarriages, the purpose of this review is to provide a survey of state-of-the-art human in vitro trophoblast models that can be used for the functional assessment of specific abnormalities/variants implicated in pregnancy loss. Since 2018, when primary human trophoblast stem cells were first derived, there has been rapid growth in models of trophoblast lineage. It has been found that a proper balance between self-renewal and differentiation in trophoblast progenitors is crucial for the maintenance of pregnancy. Different responses to aneuploidy have been shown in human embryonic and extra-embryonic lineages. Stem cell-based models provide a powerful tool to explore the effect of a specific aneuploidy/variant on the fetus through placental development, which is important, from a clinical point of view, for deciding on the suitability of embryos for transfer after preimplantation genetic testing for aneuploidy.
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spelling pubmed-92214142022-06-24 Stem Cell-Based Trophoblast Models to Unravel the Genetic Causes of Human Miscarriages Nikitina, Tatiana V. Lebedev, Igor N. Cells Review Miscarriage affects approximately 15% of clinically recognized pregnancies, and 1–3% of couples experience pregnancy loss recurrently. Approximately 50–60% of miscarriages result from chromosomal abnormalities, whereas up to 60% of euploid recurrent abortions harbor variants in candidate genes. The growing number of detected genetic variants requires an investigation into their role in adverse pregnancy outcomes. Since placental defects are the main cause of first-trimester miscarriages, the purpose of this review is to provide a survey of state-of-the-art human in vitro trophoblast models that can be used for the functional assessment of specific abnormalities/variants implicated in pregnancy loss. Since 2018, when primary human trophoblast stem cells were first derived, there has been rapid growth in models of trophoblast lineage. It has been found that a proper balance between self-renewal and differentiation in trophoblast progenitors is crucial for the maintenance of pregnancy. Different responses to aneuploidy have been shown in human embryonic and extra-embryonic lineages. Stem cell-based models provide a powerful tool to explore the effect of a specific aneuploidy/variant on the fetus through placental development, which is important, from a clinical point of view, for deciding on the suitability of embryos for transfer after preimplantation genetic testing for aneuploidy. MDPI 2022-06-14 /pmc/articles/PMC9221414/ /pubmed/35741051 http://dx.doi.org/10.3390/cells11121923 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Nikitina, Tatiana V.
Lebedev, Igor N.
Stem Cell-Based Trophoblast Models to Unravel the Genetic Causes of Human Miscarriages
title Stem Cell-Based Trophoblast Models to Unravel the Genetic Causes of Human Miscarriages
title_full Stem Cell-Based Trophoblast Models to Unravel the Genetic Causes of Human Miscarriages
title_fullStr Stem Cell-Based Trophoblast Models to Unravel the Genetic Causes of Human Miscarriages
title_full_unstemmed Stem Cell-Based Trophoblast Models to Unravel the Genetic Causes of Human Miscarriages
title_short Stem Cell-Based Trophoblast Models to Unravel the Genetic Causes of Human Miscarriages
title_sort stem cell-based trophoblast models to unravel the genetic causes of human miscarriages
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221414/
https://www.ncbi.nlm.nih.gov/pubmed/35741051
http://dx.doi.org/10.3390/cells11121923
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