F4/80+ macrophages contribute to clearance of senescent cells in the mouse postpartum uterus
Abstract
Cellular senescence, defined as an irreversible cell cycle arrest, exacerbates the tissue microenvironment. Our previous study demonstrated that mouse uterine senescent cells were physiologically increased according to gestational days and that their abnormal accumulation was linked to the onset of preterm delivery. We hypothesized that there is a mechanism for removal of senescent cells after parturition to maintain uterine function. In the current study, we noted abundant uterine senescent cells and their gradual disappearance in wild-type postpartum mice. F4/80+ macrophages were present specifically around the area rich in senescent cells. Depletion of macrophages in the postpartum mice using anti-F4/80 antibody enlarged the area of senescent cells in the uterus. We also found excessive uterine senescent cells and decreased second pregnancy success rate in a preterm birth model using uterine p53-deleted mice. Furthermore, a decrease in F4/80+ cells and an increase in CD11b+ cells with a senescence-associated inflammatory microenvironment were observed in the p53-deleted uterus, suggesting that uterine p53 deficiency affects distribution of the macrophage subpopulation, interferes with senescence clearance, and promotes senescence-induced inflammation. These findings indicate that the macrophage is a key player in the clearance of uterine senescent cells to maintain postpartum uterine function.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
F4/80+ macrophages are key players in removal of senescent uterine cells after parturition to keep postpartum uterine functionality in wild-type mice and maintain success rate of a second pregnancy in a preterm birth mouse model.
“F4/80+ macrophages are also key players in the removal of senescent uterine cells after parturition to keep postpartum uterine functionality in wild-type mice and maintain the success rate of a second pregnancy in a preterm birth mouse model [135].”
From Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases (2020) · cites this paper as [135]
Cites
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477 · see citing works
Macrophage plasticity and polarization: in vivo veritas
Sica, A., & Mantovani, A. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59643 · Cited by 6,335 · see citing works
The limited in vitro lifetime of human diploid cell strains
Hayflick, L. (1965) · Experimental Cell Research · doi:10.1016/0014-4827(65)90211-9 · Cited by 5,876 · see citing works
Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441 · see citing works
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670 · cited 2× · see citing works
“In progeroid mice as an aging model, lifelong and late-life clearance of senescent cells by a transgenic technique and drug treatment delayed age-related pathologies, clarifying the role of senescent cell clearance in the development of age-related dysfunction (9).”
BackgroundSenescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas
Xue, W., Zender, L., Miething, C., Dickins, R. A., Hernando, E., Krizhanovsky, V., Cordon-Cardo, C., & Lowe, S. W. (2007) · Nature · doi:10.1038/nature05529 · Cited by 2,473 · see citing works
The essence of senescence: Figure 1.
Kuilman, T., Michaloglou, C., Mooi, W. J., & Peeper, D. S. (2010) · Genes & Development · doi:10.1101/gad.1971610 · Cited by 2,038 · see citing works
Senescence of activated stellate cells limits liver fibrosis
Krizhanovsky, V., Yon, M., Dickins, R. A., Hearn, S., Simon, J., Miething, C., Yee, H., Zender, L., & Lowe, S. W. (2008) · Cell · doi:10.1016/j.cell.2008.06.049 · Cited by 2,029 · see citing works
Senescence of Activated Stellate Cells Limits Liver Fibrosis
Krizhanovsky, V., Yon, M., Dickins, R. A., Hearn, S., Simon, J., Miething, C., Yee, H., Zender, L., & Lowe, S. W. (2008) · Cell · doi:10.1016/j.cell.2008.09.015 · Cited by 2,027
M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination
Miron, V. E., Boyd, A., Zhao, J.-W., Yuen, T. J., Ruckh, J. M., Shadrach, J. L., van Wijngaarden, P., Wagers, A. J., Williams, A., Franklin, R. J. M., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3469 · Cited by 1,788 · see citing works
Senescence surveillance of pre-malignant hepatocytes limits liver cancer development
Kang, T.-W., Yevsa, T., Woller, N., Hoenicke, L., Wuestefeld, T., Dauch, D., Hohmeyer, A., Gereke, M., Rudalska, R., Potapova, A., et al. (2011) · Nature · doi:10.1038/nature10599 · Cited by 1,621 · see citing works
F4/80, a monoclonal antibody directed specifically against the mouse macrophage
Austyn, J. M., & Gordon, S. (1981) · European Journal of Immunology · doi:10.1002/eji.1830111013 · Cited by 1,580 · see citing works
Senescence-associated β-galactosidase is lysosomal β-galactosidase.
Lee, B. Y., Han, J. A., Im, J. S., Morrone, A., Johung, K., Goodwin, E. C., Kleijer, W. J., DiMaio, D., & Hwang, E. S. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00199.x · Cited by 1,444 · see citing works
Programmed cell senescence during mammalian embryonic development
Muñoz-Espín, D., Cañamero, M., Maraver, A., Gómez-López, G., Contreras, J., Murillo-Cuesta, S., Rodríguez-Baeza, A., Varela-Nieto, I., Ruberte, J., Collado, M., et al. (2013) · Cell · doi:10.1016/j.cell.2013.10.019 · Cited by 1,428 · see citing works
Senescence is a developmental mechanism that contributes to embryonic growth and patterning
Storer, M., Mas, A., Robert-Moreno, A., Pecoraro, M., Ortells, M. C., Di Giacomo, V., Yosef, R., Pilpel, N., Krizhanovsky, V., Sharpe, J., et al. (2013) · Cell · doi:10.1016/j.cell.2013.10.041 · Cited by 1,186 · see citing works
Senescence in tumours: evidence from mice and humans
Collado, M., & Serrano, M. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2772 · Cited by 1,124 · see citing works
Jonkers, J., Meuwissen, R. L. J., van der Gulden, H. M. L., Peterse, H. L., van der Valk, M., & Berns, A. J. M. (2001) · Nature Genetics · doi:10.1038/ng747 · Cited by 1,053 · see citing works
Non-Cell-Autonomous Tumor Suppression by p53
Lujambio, A., Akkari, L., Simon, J., Grace, D., Tschaharganeh, D. F., Bolden, J. E., Zhao, Z., Thapar, V., Joyce, J. A., Krizhanovsky, V., et al. (2013) · Cell · doi:10.1016/j.cell.2013.03.020 · Cited by 766 · cited 4× · see citing works
“eases owing to failure of tissue remodeling (9, 37).”
BackgroundResultInfluentialCicinelli, E., Matteo, M., Tinelli, R., Lepera, A., Alfonso, R., Indraccolo, U., Marrocchella, S., Greco, P., & Resta, L. (2014) · Human Reproduction · doi:10.1093/humrep/deu292 · Cited by 525 · see citing works
Coppé, J.-P., Patil, C. K., Rodier, F., Krtolica, A., Beauséjour, C. M., Parrinello, S., Hodgson, J. G., Chin, K., Desprez, P.-Y., & Campisi, J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009188 · Cited by 455 · see citing works
Rapid categorization of natural face images in the infant right hemisphere
de Heering, A., & Rossion, B. (2015) · eLife · doi:10.7554/elife.06564 · Cited by 428 · see citing works
Lee, S. H., Starkey, P. M., & Gordon, S. (1985) · The Journal of Experimental Medicine · doi:10.1084/jem.161.3.475 · Cited by 423 · see citing works
Johnston-MacAnanny, E. B., Hartnett, J., Engmann, L. L., NULSEN, J. C., Sanders, M. M., & Benadiva, C. A. (2009) · Fertility and Sterility · doi:10.1016/j.fertnstert.2008.12.131 · Cited by 420 · see citing works
Lung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice
Bedoret, D., Wallemacq, H., Marichal, T., Desmet, C., Quesada Calvo, F., Henry, E., Closset, R., Dewals, B., Thielen, C., Gustin, P., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci39717 · Cited by 399 · see citing works
Recurrent turnover of senescent cells during regeneration of a complex structure
Yun, M. H., Davaapil, H., & Brockes, J. P. (2015) · eLife · doi:10.7554/elife.05505 · Cited by 385 · see citing works
Cre-mediated recombination in cell lineages that express the progesterone receptor
Soyal, S. M., Mukherjee, A., Lee, K. Y.-S., Li, J., Li, H., DeMayo, F. J., & Lydon, J. P. (2005) · genesis · doi:10.1002/gene.20098 · Cited by 380 · see citing works
Tidball, J. G., & Wehling‐Henricks, M. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2006.118265 · Cited by 375 · see citing works
Bouet, P.-E., El Hachem, H., Monceau, E., Gariépy, G., Kadoch, I.-J., & Sylvestre, C. (2016) · Fertility and Sterility · doi:10.1016/j.fertnstert.2015.09.025 · Cited by 335 · see citing works
Clausen, B. H., Lambertsen, K. L., Babcock, A. A., Holm, T. H., Dagnæs‐Hansen, F., & Finsen, B. R. (2008) · Journal of Neuroinflammation · doi:10.1186/1742-2094-5-46 · Cited by 315 · see citing works
Coppé, J.-P., Patil, C. K., Rodier, F., Sun, Y., Muñoz, D. P., Goldstein, J., Nelson, P. S., Desprez, P.-Y., & Campisi, J. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060301 · Cited by 302 · see citing works
Hirota, Y., Daikoku, T., Tranguch, S. L., Xie, H., Bradshaw, H. B., & Dey, S. K. (2010) · Journal of Clinical Investigation · doi:10.1172/jci40051 · Cited by 235 · see citing works
Self-citationYang, R. J., Du, X., Wang, Y., Song, X., Yang, Y., & Qiao, J. (2014) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-013-3131-2 · Cited by 155 · see citing works
Maternal hypoxia activates endovascular trophoblast cell invasion
Rosario, G. X., Konno, T., & Soares, M. J. (2008) · Developmental Biology · doi:10.1016/j.ydbio.2007.12.007 · Cited by 153 · see citing works
Martínez‐Pomares, L., Reid, D. M., Brown, G. D., Taylor, P. R., Stillion, R. J., Linehan, S. A., ZAMZE, S. E., Gordon, S., & Wong, S. Y. C. (2003) · Journal of Leukocyte Biology · doi:10.1189/jlb.0902450 · Cited by 139 · see citing works
Hirota, Y., Cha, J., Yoshie, M., Daikoku, T., & Dey, S. K. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1108180108 · Cited by 125 · see citing works
Self-citationDelgado, S. R., McBey, B.-A., Yamashiro, S., et al. (1996) · Journal of Leukocyte Biology · doi:10.1002/jlb.59.2.262 · Cited by 104 · see citing works
Differential senescence in feto-maternal tissues during mouse pregnancy
Bonney, E. A., Krebs, K., Saade, G., Kechichian, T., Trivedi, J., Huaizhi, Y., & Menon, R. (2016) · Placenta · doi:10.1016/j.placenta.2016.04.018 · Cited by 86 · see citing works
P53 coordinates decidual sestrin 2/AMPK/mTORC1 signaling to govern parturition timing
Deng, W., Cha, J., Yuan, J., Haraguchi, H., Bartos, A., Leishman, E., Viollet, B., Bradshaw, H. B., Hirota, Y., & Dey, S. K. (2016) · Journal of Clinical Investigation · doi:10.1172/jci87715 · Cited by 85 · see citing works
Self-citationCombinatory approaches prevent preterm birth profoundly exacerbated by gene-environment interactions
Cha, J., Bartos, A., Egashira, M., Haraguchi, H., Saito‐Fujita, T., Leishman, E., Bradshaw, H. B., Dey, S. K., & Hirota, Y. (2013) · Journal of Clinical Investigation · doi:10.1172/jci70098 · Cited by 83 · see citing works
Self-citationVanadium pentoxide induces pulmonary inflammation and tumor promotion in a strain-dependent manner
Rondini, E. A., Walters, D. M., & Bauer, A. K. (2010) · Particle and Fibre Toxicology · doi:10.1186/1743-8977-7-9 · Cited by 80 · see citing works
Hiraoka, T., Hirota, Y., Saito‐Fujita, T., Matsuo, M., Egashira, M., Matsumoto, L., Haraguchi, H., Dey, S. K., Furukawa, K. S., Fujii, T., et al. (2016) · JCI Insight · doi:10.1172/jci.insight.87591 · Cited by 68 · see citing works
Self-citationThin endometrium transcriptome analysis reveals a potential mechanism of implantation failure
Maekawa, R., Taketani, T., Mihara, Y., Sato, S., Okada, M., Tamura, I., Jozaki, K., Kajimura, T., Asada, H., Tamura, H., et al. (2017) · Reproductive Medicine and Biology · doi:10.1002/rmb2.12030 · Cited by 67 · see citing works
Haraguchi, H., Saito‐Fujita, T., Hirota, Y., Egashira, M., Matsumoto, L., Matsuo, M., Hiraoka, T., Koga, K., Yamauchi, N., Fukayama, M., et al. (2014) · Molecular Endocrinology · doi:10.1210/me.2014-1097 · Cited by 66 · see citing works
Self-citationLinehan, S. A., Coulson, P. S., Wilson, R. A., Mountford, A. P., Brombacher, F., Martínez‐Pomares, L., & Gordon, S. (2003) · Laboratory Investigation · doi:10.1097/01.lab.0000081392.93701.6f · Cited by 57 · see citing works
The Role of Inflammatory Pathways in Implantation Failure: Chronic Endometritis and Hydrosalpinges
Akopians, A. L., Pisarska, M. D., & Wang, E. T. (2015) · Seminars in Reproductive Medicine · doi:10.1055/s-0035-1554916 · Cited by 42 · see citing works
Rommer, A., Steinmetz, B., Herbst, F., Hackl, H., Heffeter, P., Heilos, D., Filipits, M., Steinleitner, K., Hemmati, S., Herbacek, I., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0056308 · Cited by 24 · see citing works
Sawada, M., Wilkinson, J. M., McAdoo, D. J., et al. (1976) · Journal of Neurobiology · doi:10.1002/neu.480070506 · Cited by 18 · see citing works
Hwang, S. E., Kim, J. H., Yu, H. C., et al. (2014) · The Anatomical Record · doi:10.1002/ar.22940 · Cited by 14 · see citing works
TIMING OF LH RELEASE AND OVULATION IN THE POST PARTUM MOUSE
Bingel, A. S., & Schwartz, N. B. (1969) · Reproduction · doi:10.1530/jrf.0.0190231 · Cited by 10 · see citing works
Lee, J. H., Cho, Y. I., Choi, S. S., et al. (2016) · Journal of Visualized Experiments · doi:10.3791/53696 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Senescent cell clearance by the immune system: Emerging therapeutic opportunities
Prata, L. G. P. L., Ovsyannikova, I. G., Tchkonia, T., & Kirkland, J. L. (2018) · Seminars in Immunology · doi:10.1016/j.smim.2019.04.003 · Cited by 497 · see citing works
Role of immune cells in the removal of deleterious senescent cells
Kale, A., Sharma, A., Stolzing, A., Desprez, P.-Y., & Campisi, J. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-00187-9 · Cited by 351 · see citing works
Cellular Senescence in the Kidney
Docherty, M.-H., O’Sullivan, E. D., Bonventre, J. V., & Ferenbach, D. A. (2019) · Journal of the American Society of Nephrology · doi:10.1681/asn.2018121251 · Cited by 291 · see citing works
Cellular senescence: Immunosurveillance and future immunotherapy
Burton, D. G. A., & Stolzing, A. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.02.001 · Cited by 221 · see citing works
Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases
Song, P., An, J., & Zou, M.-H. (2020) · Cells · doi:10.3390/cells9030671 · Cited by 198 · see citing works
“F4/80+ macrophages are also key players in the removal of senescent uterine cells after parturition to keep postpartum uterine functionality in wild-type mice and maintain the success rate of a second pregnancy in a preterm birth mouse model [135].”
BackgroundSimilarities and interplay between senescent cells and macrophages
Behmoaras, J., & Gil, J. (2021) · Journal of Cell Biology · doi:10.1083/jcb.202010162 · Cited by 158 · see citing works
Narzt, M.-S., Pils, V., Kremslehner, C., Nagelreiter, I.-M., Schosserer, M., Bessonova, E., Bayer, A., Reifschneider, R., Terlecki-Zaniewicz, L., Waidhofer-Söllner, P., et al. (2021) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2020.11.020 · Cited by 73 · see citing works
Innate immunity and cellular senescence: The good and the bad in the developmental and aged brain
Santoro, A., Spinelli, C. C., Martucciello, S., Nori, S. L., Capunzo, M., Puca, A. A., & Ciaglia, E. (2018) · Journal of Leukocyte Biology · doi:10.1002/jlb.3mr0118-003r · Cited by 50 · see citing works
Context‐dependent roles of cellular senescence in normal, aged, and disease states
Moiseeva, V., Cisneros, A., Cobos, A. C., Tarrega, A. B., Oñate, C. S., Perdiguero, E., Serrano, A. L., & Muñoz‐Cánoves, P. (2023) · The FEBS Journal · doi:10.1111/febs.16573 · Cited by 34 · see citing works
- Authors
- Egashira, M., Hirota, Y., Shimizu-Hirota, R., Saito-Fujita, T., Haraguchi, H., Matsumoto, L., Matsuo, M., Hiraoka, T., Tanaka, T., Akaeda, S., Takehisa, C., Saito-Kanatani, M., Maeda, K.-I., Fujii, T., & Osuga, Y.
- Affiliations
- The University of Tokyo (JP)
- Japan Science and Technology Agency (JP)
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2017-05-18
- Volume
- 158
- Issue
- 7
- Pages
- 2344-2353
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2616605368
- Cited by
- 90
- References
- 50
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 13 · 2023: 11 · 2022: 11 · 2021: 10 · 2020: 11 · 2019: 7 · 2018: 7
- FWCI
- 5.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (16K15701, 16K15700, 17K16833, 16H06279, 15J40160, 15K10660, 17H06640, 16K10668, 16H05469, 16H04679)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Health Sciences › Medicine › Epidemiology › Preterm Birth and Chorioamnionitis
- Keywords
- cellular senescence, senescent cell clearance, F4/80+ macrophages, postpartum uterus, uterine macrophages, p53 deficiency, senescence-associated inflammation, preterm birth, CD11b+ macrophages, macrophage depletion, uterine function, pregnancy success
- MeSH terms
- Animals, Antigens, Differentiation, Female, Macrophages, Male, Mice, Inbred ICR, Mice, Transgenic, Pregnancy, Uterus, Genes, p53, Cellular Senescence, Postpartum Period, Mice, Cytophagocytosis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
