Entosis Allows Timely Elimination of the Luminal Epithelial Barrier for Embryo Implantation
Open accessAbstract
During implantation, uterine luminal epithelial (LE) cells first interact with the blastocyst trophectoderm. Within 30 hr after the initiation of attachment, LE cells surrounding the blastocyst in the implantation chamber (crypt) disappear, allowing trophoblast cells to make direct physical contact with the underneath stroma for successful implantation. The mechanism for the extraction of LE cells was thought to be mediated by apoptosis. Here, we show that LE cells in direct contact with the blastocyst are endocytosed by trophoblast cells by adopting the nonapoptotic cell-in-cell invasion process (entosis) in the absence of caspase 3 activation. Our in vivo observations were reinforced by the results of co-culture experiments with primary uterine epithelial cells with trophoblast stem cells or blastocysts showing internalization of epithelial cells by trophoblasts. We have identified entosis as a mechanism to remove LE cells by trophoblast cells in implantation, conferring a role for entosis in an important physiological process.
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Entosis does not always lead to death of invading cells within the lysosome; entotic cells can remain viable and proliferate inside host cells or upon escape.
“entosis does not always lead to the death of invading cells within the lysosome. Thus, at least in some circumstances, entotic cells remain viable and even proliferate inside host cells or upon escape [716].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [716]
In mammalian embryo implantation, trophoblast cells reportedly eliminate uterine luminal epithelial cells upon entosis.
“in the course of mammalian embryo implantation, trophoblast cells reportedly eliminate uterine luminal epithelial cells upon entosis [716].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [716]
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- Authors
- Li, Y., Sun, X., & Dey, S. K.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- Corresponding author
- Sun, Xiaofei
- Dey, Sudhansu K.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 11
- Issue
- 3
- Pages
- 358-365
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5089169
- OpenAlex
- W2094728839
- Cited by
- 155
- References
- 25
- Citations by year
- 2026: 11 · 2025: 20 · 2024: 14 · 2023: 12 · 2022: 17 · 2021: 15 · 2020: 8 · 2019: 18 · 2018: 13 · 2017: 16 · 2016: 7 · 2015: 4
- FWCI
- 6.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- March of Dimes Foundation
- National Institutes of Health
- National Institute on Drug Abuse (R01DA006668, R37DA006668, DA006668)
- National Cancer Institute (P01CA7783)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD068524, R01HD068524)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Keywords
- entosis, embryo implantation, uterine luminal epithelium, trophoblast, blastocyst, caspase-3, trophoblast stem cells, endocytosis
- MeSH terms
- Animals, Epithelial Cells, Female, Embryo Implantation, Pregnancy, Uterus, Coculture Techniques, In Situ Nick-End Labeling, Mice, Entosis
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