The morphology of various types of cell death in prenatal tissues
Abstract
The morphology of physiological cell death and of necroses caused by treatment with various embryotoxic substances (cyclophosphamide, actinomycin D, vitamin A, vincristine, 6‐aminonicotinamide, 6‐mercaptopurine) and Mg deficiency were studied electron microscopically in rat and mouse embryos and fetuses. Three types of necroses were distinguished in control tissues. (1) Condensation and fragmentation of single cells undergoing phagocytosis, with lysosomal disintegration of the fragments in neighboring cells. (2) Primary formation of lysosomes in dying cells, with activation and subsequent destruction and phagocytosis of the fragments by neighboring cells. This type of cell death in most instances was found during destruction of organs and large cell units. (3) Disintegration of cells into fragments, which were optically no longer detectable, without involvement of the lysosomal system, e.g., in embryonic and epiphyseal cartilage before ossification. In cases of embryolethal toxic agents, e.g., Mg deficiency, cell necroses of large areas prevailed, which were characterized by typical pyknoses (rough, dense chromatin) and lack of lysosomes. In the case of teratogenic effects, however, substances that disturb replication, transcription, and translation (cyclophosphamide, actinomycin D, 6‐mercaptopurine) caused an increase in the number of necroses of type 1. It can, therefore, be assumed that under these conditions similar processes take place in physiological and experimentally induced necroses. After administration of vitamin A, labilization of lysosomes and necroses of type 2 were observed.
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Cell death has historically been classified into three morphological forms: type I apoptosis, type II autophagy, and type III necrosis.
“Together with the mechanisms whereby dead cells and their fragments are disposed of, such morphotypes have historically been employed to classify cell death into three different forms: (1) type I cell death or apoptosis, exhibiting cytoplasmic shrinkage, chromatin condensation (pyknosis), nuclear fragmentation (karyorrhexis), and plasma membrane blebbing, culminating with the formation of apparent”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [23]
Cites
Saunders, J. W. (1966) · Science · doi:10.1126/science.154.3749.604 · Cited by 955 · see citing works
Tata, J. R. (1966) · Developmental Biology · doi:10.1016/0012-1606(66)90050-9 · Cited by 361 · see citing works
Ultrastructural aspects of early development of the fore-limb buds in the chick and the mouse
JURAND, A. (1965) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.1965.0045 · Cited by 139 · see citing works
Ballard, K. J., & Holt, S. J. (1968) · Journal of Cell Science · doi:10.1242/jcs.3.2.245 · Cited by 129 · see citing works
Über Untergang von Zellen während der normalen Entwicklung bei Wirbeltieren
Ernst, M. (1926) · Anatomy and Embryology · doi:10.1007/bf02118264 · Cited by 121 · see citing works
Cell death in normal development.
Glucksmann, A. (1965) · PubMed · Cited by 106 · see citing works
Fallon, J. F., & Saunders, J. W. (1968) · Developmental Biology · doi:10.1016/0012-1606(68)90026-2 · Cited by 97 · see citing works
DEVELOPMENT OF THE NERVOUS SYSTEM
Hamburger, V. (1952) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1952.tb26527.x · Cited by 95 · see citing works
Weber, R. H. (2008) · Novartis Foundation symposium · doi:10.1002/9780470715314.ch11 · Cited by 73 · see citing works
Studies on possible mechanisms of programmed cell death in the chick embryo
Webster, D. A., & Gross, J. (1970) · Developmental Biology · doi:10.1016/0012-1606(70)90012-6 · Cited by 72 · see citing works
Über die Bedeutung von Zellvorgängen für die Formbildung epithelialer Organe
Glucksmann, A. (1930) · Anatomy and Embryology · doi:10.1007/bf02117845 · Cited by 62 · see citing works
The Epithelium-Connective Tissue Interface During Closure of the Secondary Palate in Rodent Embryos
Farbman, A. I. (1969) · Journal of Dental Research · doi:10.1177/00220345690480050201 · Cited by 40 · see citing works
Growth kinetics of mammalian embryos during the stage of differentiation
K�hler, E., Merker, H.-J., Ehmke, W., et al. (1972) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf00508767 · Cited by 35 · see citing works
Self-citationLa régression de la glande mammaire à l'arrêt de la lactation
Verley, J. M., & Hollmann, K. (1967) · Cell and Tissue Research · doi:10.1007/bf01901702 · Cited by 30 · see citing works
Wolff, É. (1953) · Cellular and Molecular Life Sciences · doi:10.1007/bf02154578 · Cited by 25 · see citing works
Elektronenmikroskopische Untersuchungen an Lysosomen im Blastem der Extremit�tenknospe der Ratte
Schwarz, W. (1966) · Cell and Tissue Research · doi:10.1007/bf00348465 · Cited by 25 · see citing works
Schweichel, J. U. (1972) · PubMed · Cited by 23 · see citing works
Self-citation[The regression of mammary glands at the end of lactation. II. Electron microscopic study].
Hollmann, K., & Verley, J. M. (1967) · PubMed · Cited by 23 · see citing works
Goldblatt, P. J., Verbin, R. S., & Sullivan, R. J. (1970) · Experimental Cell Research · doi:10.1016/0014-4827(70)90338-1 · Cited by 21 · see citing works
Schweichel, J. U. (1972) · Anatomy and Embryology · doi:10.1007/bf00519177 · Cited by 20 · see citing works
Self-citationLinsenentwicklung und Peridermbildung
Glucksmann, A. (1930) · Anatomy and Embryology · doi:10.1007/bf02117846 · Cited by 19 · see citing works
Forsberg, J. (1961) · PubMed · Cited by 18 · see citing works
Zur Rückbildung embryonaler Anlagen
Nassbaum, M. (1901) · Archiv für Mikroskopische Anatomie · doi:10.1007/bf02976185 · Cited by 14 · see citing works
Cassier, P., & Fain‐Maurel, M. (1970) · Journal of Insect Physiology · doi:10.1016/0022-1910(70)90172-1 · Cited by 11 · see citing works
The Death of Cells in Normal Multicellular Organisms
Biggers, J. D. (1964) · Novartis Foundation symposium · doi:10.1002/9780470719336.ch14 · Cited by 8 · see citing works
Studies on the teratogenic phase specificity of actinomycin D in the rat
K�hler, E., & Merker, H. J. (1972) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf00505066 · Cited by 6 · see citing works
Self-citationMerker, H. J., K�hler, E., Neuber, T., et al. (1968) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf00537986 · Cited by 4 · see citing works
Self-citationNoack, W. (1972) · Acta Neuropathologica · doi:10.1007/bf00687549 · Cited by 3 · see citing works
Elektronenmikroskopische Untersuchungen an einigen Rattenorganen im Mg-Mangelzustand
Merker, H. J., & Günther, T. (1970) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.1970.8.1.71 · Cited by 2 · see citing works
Self-citationBorowski, R. (1973) · Anatomy and Embryology · doi:10.1007/bf00520718 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680 · see citing works
Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009
Kroemer, G., Galluzzi, L., Vandenabeele, P., Abrams, J., Alnemri, E. S., Baehrecke, E. H., Blagosklonny, M. V., El-Deiry, W. S., Golstein, P., Green, D. R., et al. (2009) · Cell Death & Differentiation · doi:10.1038/cdd.2008.150 · Cited by 3,399 · see citing works
Cell death during development of the nervous system
Oppenheim, R. W. (1991) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.14.030191.002321 · Cited by 3,084 · see citing works
Galluzzi, L., Vitale, I., Abrams, J. M., Alnemri, E. S., Baehrecke, E. H., Blagosklonny, M. V., Dawson, T. M., Dawson, V. L., El-Deiry, W. S., Fulda, S., et al. (2012) · Cell Death & Differentiation · doi:10.1038/cdd.2011.96 · Cited by 2,421 · see citing works
Molecular mechanisms of necroptosis: an ordered cellular explosion
Vandenabeele, P., Galluzzi, L., Vanden Berghe, T., & Kroemer, G. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2970 · Cited by 2,382 · see citing works
Regulated necrosis: the expanding network of non-apoptotic cell death pathways
Berghe, T. V., Linkermann, A., Jouan-Lanhouet, S., Walczak, H., & Vandenabeele, P. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3737 · Cited by 1,735 · see citing works
Molecular definitions of autophagy and related processes
Galluzzi, L., Baehrecke, E. H., Ballabio, A., Boya, P., Bravo‐San Pedro, J. M., Cecconi, F., Choi, A. M., Chu, C. T., Codogno, P., Colombo, M. I., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201796697 · Cited by 1,646 · see citing works
Crosstalk between apoptosis.; necrosis and autophagy
Nikoletopoulou, V., Markaki, M., Palikaras, K., & Tavernarakis, N. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.06.001 · Cited by 1,366 · see citing works
Essential versus accessory aspects of cell death: recommendations of the NCCD 2015
Galluzzi, L., Bravo-San Pedro, J. M., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Alnemri, E. S., Altucci, L., Andrews, D., Annicchiarico-Petruzzelli, M., et al. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2014.137 · Cited by 1,002 · see citing works
Autophagy-dependent cell death
Denton, D., & Kumar, S. (2019) · Cell Death & Differentiation · doi:10.1038/s41418-018-0252-y · Cited by 777 · see citing works
Festjens, N., Vanden Berghe, T., & Vandenabeele, P. (2006) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2006.06.014 · Cited by 710 · see citing works
Growth Arrest and Autophagy Are Required for Salivary Gland Cell Degradation in Drosophila
Berry, D. L., & Baehrecke, E. H. (2007) · Cell · doi:10.1016/j.cell.2007.10.048 · Cited by 602 · see citing works
Initiation and execution mechanisms of necroptosis: an overview
Grootjans, S., Vanden Berghe, T., & Vandenabeele, P. (2017) · Cell Death & Differentiation · doi:10.1038/cdd.2017.65 · Cited by 566 · see citing works
Lefranc, F., Facchini, V., & Kiss, R. (2007) · The Oncologist · doi:10.1634/theoncologist.12-12-1395 · Cited by 237 · see citing works
Liao, G., Yao, Y., Liu, J., Yu, Z., Cheung, S., Xie, A., Liang, X., & Bi, X. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.070052 · Cited by 220 · see citing works
Lysosomal cell death mechanisms in aging
Gómez-Sintes, R., Ledesma, M. D., & Boya, P. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.02.009 · Cited by 216 · see citing works
Genetic Control of Programmed Cell Death During Animal Development
Conradt, B. (2009) · Annual Review of Genetics · doi:10.1146/annurev.genet.42.110807.091533 · Cited by 173 · see citing works
Innate Immune Response in Retinal Homeostasis and Inflammatory Disorders
Murakami, Y., Ishikawa, K., Nakao, S., & Sonoda, K.-H. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2019.100778 · Cited by 125 · see citing works
Eaten alive: novel insights into autophagy from multicellular model systems
Zhang, H., & Baehrecke, E. H. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.03.001 · Cited by 102 · see citing works
Dysregulated autophagy contributes to caspase-dependent neuronal apoptosis
Chung, Y., Lee, J., Jung, S., Lee, Y., Cho, J. W., & Oh, Y. J. (2018) · Cell Death & Disease · doi:10.1038/s41419-018-1229-y · Cited by 99 · see citing works
Non-apoptotic cell death in animal development
Kutscher, L. M., & Shaham, S. (2017) · Cell Death & Differentiation · doi:10.1038/cdd.2017.20 · Cited by 67 · see citing works
Lippai, M., Csikós, G., Maróy, P., Lukácsovich, T., Juhász, G., & Sass, M. (2008) · Autophagy · doi:10.4161/auto.5719 · Cited by 56 · see citing works
The Proton-Coupled Monocarboxylate Transporter Hermes Is Necessary for Autophagy during Cell Death
Velentzas, P. D., Zhang, L., Das, G., Chang, T.-K., Nelson, C., Kobertz, W. R., & Baehrecke, E. H. (2018) · Developmental Cell · doi:10.1016/j.devcel.2018.09.015 · Cited by 31 · see citing works
- Authors
- Schweichel, J. ‐., & Merker, H. ‐.
- Affiliations
- Freie Universität Berlin (DE)
- Venue
- Teratology
- Publisher
- Wiley
- Published
- 1973-06
- Volume
- 7
- Issue
- 3
- Pages
- 253-266
- ISSN
- 0040-3709 (ISSN-L)
- 1096-9926
- OpenAlex
- W2046205790
- Cited by
- 738
- References
- 30
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 15 · 2023: 25 · 2022: 17 · 2021: 19 · 2020: 25 · 2019: 20 · 2018: 25 · 2017: 20 · 2016: 27 · 2015: 22 · 2014: 33 · 2013: 29 · 2012: 26
- FWCI
- 1.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Teratology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Keywords
- cell death, necrosis, physiological cell death, embryotoxicity, teratogenicity, lysosomes, phagocytosis, cyclophosphamide, actinomycin D, vitamin A, vincristine, 6-aminonicotinamide, 6-mercaptopurine, hypomagnesemia, pyknosis, cartilage, rat embryo, mouse embryo
- MeSH terms
- Abnormalities, Drug-Induced, Animals, Cell Survival, Cyclophosphamide, Dactinomycin, Embryo, Mammalian, Female, Embryonic and Fetal Development, Fetus, Magnesium Deficiency, Mice, Inbred Strains, Microscopy, Electron, Necrosis, Niacinamide, Pregnancy, Rats, Inbred Strains, Vincristine, Vitamin A, Mercaptopurine, Mice, Rats
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