Apoptosis and Related Proteins in Placenta of Intrauterine Fetal Death in Prostaglandin F Receptor-Deficient Mice1
Abstract
The present study investigated whether the increase of apoptosis in the placenta is associated with intrauterine fetal death in prostaglandin F receptor-deficient mice. Apoptosis was demonstrated within placental and decidual tissue by the TUNEL method. The majority of apoptosis was found in syncytiotrophoblast tissues. Enhanced TUNEL-positive staining in the syncytiotrophoblast layer was scattered in the placental tissues in clusters of apoptotic cells in the death group. Marked TUNEL-positive cells were identified in decidua of both groups. The rate of apoptosis in the placenta and decidua in the death group was higher than that in the survival group (P < 0.05). Immunohistochemical analysis showed that the level of active caspase-3 protein expression in the placenta in the death group was much higher than that in the survival group. The level of Bcl-2 protein expression in the placenta in the death group was much lower than that in the survival group. Western blot analysis demonstrated that increased expression of the active form of caspase-3 was detected in the placenta and decidua in the death group compared with that in the survival group. In contrast, a decrease in the expression of Bcl-2 was detected in the placenta and decidua in the death group compared with that in the survival group. Enhanced expression of Bax:Bcl-2 ratio was detected in placenta and decidua in the death group compared with that in the survival group. Thus, significantly increased apoptosis in the mouse placenta and decidua might be involved in the pathophysiologic mechanism of intrauterine fetal death.
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Apoptosis at the decidual/uterine interface allows initial separation of the maternal/placental unit at the time of parturition.
“putatively allowing for initial separation of the maternal/placental unit at the time of parturition40–43.”
From Conditional loss of ERK1 and ERK2 results in abnormal placentation and delayed parturition in the mouse (2019) · cites this paper as [41]
Cites
Green, D. R., & Reed, J. C. (1998) · Science · doi:10.1126/science.281.5381.1309 · Cited by 8,998 · see citing works
Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death
Oltval, Z. N., Milliman, C. L., & Korsmeyer, S. J. (1993) · Cell · doi:10.1016/0092-8674(93)90509-o · Cited by 6,003 · see citing works
The Bcl-2 Protein Family: Arbiters of Cell Survival
Adams, J. M., & Cory, S. (1998) · Science · doi:10.1126/science.281.5381.1322 · Cited by 5,303 · see citing works
Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells
Vaux, D., Cory, S., & Adams, J. (1988) · Nature · doi:10.1038/335440a0 · Cited by 3,355 · see citing works
Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours
Graeber, T. G., Osmanian, C., Jacks, T., Housman, D. E., Koch, C. J., Lowe, S. W., & Giaccia, A. J. (1996) · Nature · doi:10.1038/379088a0 · Cited by 2,300 · see citing works
Involvement of the bcl -2 Gene in Human Follicular Lymphoma
Tsujimoto, Y., Cossman, J., Jaffe, E. S., & Croce, C. M. (1985) · Science · doi:10.1126/science.3874430 · Cited by 1,787 · see citing works
The proto-oncogene Bcl-2 and its role in regulating apoptosis
Kroemer, G. (1997) · Nature Medicine · doi:10.1038/nm0697-614 · Cited by 1,739 · see citing works
Double identity for proteins of the Bcl-2 family
Reed, J. C. (1997) · Nature · doi:10.1038/42867 · Cited by 1,494 · see citing works
BCL2 protein is topographically restricted in tissues characterized by apoptotic cell death.
Hockenbery, D. M., Zutter, M., Hickey, W., Nahm, M., & Korsmeyer, S. J. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.16.6961 · Cited by 1,252 · cited 1× · see citing works
“Overexpression of Bax promotes apoptotic cell death, and conversely, Bcl-2 promotes this type of cell survival [15, 16].”
BackgroundGreen, D. R. (1998) · Cell · doi:10.1016/s0092-8674(00)81728-6 · Cited by 1,193 · see citing works
Reed, J. C. (1998) · Oncogene · doi:10.1038/sj.onc.1202591 · Cited by 1,057 · see citing works
Advances in ultrasound biomicroscopy
Foster, F. S., Pavlin, C. J., Harasiewicz, K. A., Christopher, D. A., & Turnbull, D. H. (2000) · Ultrasound in Medicine & Biology · doi:10.1016/s0301-5629(99)00096-4 · Cited by 720 · see citing works
Failure of Parturition in Mice Lacking the Prostaglandin F Receptor
Sugimoto, Y., Yamasaki, A., Segi, E., Tsuboi, K., Aze, Y., Nishimura, T., Oida, H., Yoshida, N., Tanaka, T., Katsuyama, M., et al. (1997) · Science · doi:10.1126/science.277.5326.681 · Cited by 608 · cited 4× · see citing works
“Therefore, this PGF2a receptor-deficient mouse provides a good animal model for studying intrauterine fetal death in postterm pregnancy [10, 19].”
BackgroundMethodResultInfluentialSelf-citationIshihara, N., Matsuo, H., Murakoshi, H., Laoag‐Fernandez, J. B., Samoto, T., & Maruo, T. (2002) · American Journal of Obstetrics and Gynecology · doi:10.1067/mob.2002.119176 · Cited by 509 · see citing works
Hetts, S. W. (1998) · JAMA · doi:10.1001/jama.279.4.300 · Cited by 506 · see citing works
Placental apoptosis in preeclampsia
Allaire, A. D. (2000) · Obstetrics and Gynecology · doi:10.1016/s0029-7844(00)00895-4 · Cited by 416 · see citing works
Villous cytotrophoblast regulation of the syncytial apoptotic cascade in the human placenta
Huppertz, B., Frank, H., Kingdom, J. C., Reister, F., & Kaufmann, P. (1998) · Histochemistry and Cell Biology · doi:10.1007/s004180050311 · Cited by 400 · see citing works
Placental apoptosis in normal human pregnancy
SMITH, S. C. H., Baker, P. N., & SYMONDS, E. M. (1997) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(97)70438-1 · Cited by 400 · see citing works
Increased placental apoptosis in intrauterine growth restriction
SMITH, S. C. H., Baker, P. N., & SYMONDS, E. M. (1997) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(97)70081-4 · Cited by 374 · see citing works
APOPTOSIS AND DISEASE: Regulation and Clinical Relevance of Programmed Cell Death
Rudin, C. M., & Thompson, C. B. (1997) · Annual Review of Medicine · doi:10.1146/annurev.med.48.1.267 · Cited by 354 · see citing works
DiFederico, E., Genbacev, O., & Fisher, S. J. (1999) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)65123-1 · Cited by 348 · see citing works
Increased placental apoptosis in pregnancies complicated by preeclampsia
Leung, D. N., Smith, S. C., To, K. F., Sahota, D. S., & Baker, P. N. (2001) · American Journal of Obstetrics and Gynecology · doi:10.1067/mob.2001.112906 · Cited by 281 · see citing works
Histological and fine structural observations on the placenta of the rat
Davies, J., & Glasser, S. R. (2008) · Acta Anatomica · doi:10.1159/000143100 · Cited by 270 · see citing works
Nelson, D. M. (1996) · Placenta · doi:10.1016/s0143-4004(96)90019-3 · Cited by 194 · see citing works
Divon, M. Y., Haglund, B., Nisell, H., Otterblad, P. O., & Westgren, M. (1998) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(98)70482-x · Cited by 185 · see citing works
Kokawa, K., Shikone, T., & Nakano, R. (1998) · Placenta · doi:10.1016/s0143-4004(98)90094-7 · Cited by 140 · see citing works
Apoptosis in the Brains of Infants Suffering Intrauterine Cerebral Injury
Edwards, A. D., Yue, X., Cox, P. M., Hope, P. L., Azzopardi, D., Squier, M. V., & Mehmet, H. (1997) · Pediatric Research · doi:10.1203/00006450-199711000-00022 · Cited by 124 · see citing works
CURRENT TOPIC: To Be, or Not to Be, That is the Question. Apoptosis in Human Trophoblast
Levy, R., & Nelson, D. M. (2000) · Placenta · doi:10.1053/plac.1999.0450 · Cited by 120 · see citing works
Role of rostaglandins in reproduction
Goldberg, V. J., & Ramwell, P. W. (1975) · Physiological Reviews · doi:10.1152/physrev.1975.55.3.325 · Cited by 111 · see citing works
Apoptosis in decidual tissue regression and reorganization
Gu, Y., Jow, G., Moulton, B. C., Lee, C., Sensibar, J. A., Park-Sarge, O.-K., Chen, T. J., & Gibori, G. (1994) · Endocrinology · doi:10.1210/endo.135.3.8070373 · Cited by 110 · see citing works
Ratts, V. S., Tao, X.-J., Webster, C., Swanson, P. E., Smith, S. D., Brownbill, P., Krajewski, S., Reed, J. C., Tilly, J. L., & Nelson, D. M. (2000) · Placenta · doi:10.1053/plac.1999.0486 · Cited by 108 · see citing works
Stähelin, B. J., Marti, U., Solioz, M., Zimmermann, H., & Reichen, J. (1998) · Molecular Pathology · doi:10.1136/mp.51.4.204 · Cited by 104 · see citing works
The immunolocalization of bcl-2 at the maternal-fetal interface in healthy and failing pregnancies
Lea, R. G., Al-sharekh, N., Tulppala, M., & Critchley, H. (1997) · Human Reproduction · doi:10.1093/humrep/12.1.153 · Cited by 78 · see citing works
Qiao, S., Nagasaka, T., Harada, T., & Nakashima, N. (1998) · Placenta · doi:10.1016/s0143-4004(98)90075-3 · Cited by 75 · see citing works
[The role of prostaglandins in reproduction].
Serban, A. M. (1972) · PubMed · Cited by 71 · see citing works
Placental apoptosis is increased in post‐term pregnancies
SMITH, S. C. H., & Baker, P. N. (1999) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.1999.tb08410.x · Cited by 66 · see citing works
Effect of decidualization on the expression of bax and bcl-2 in the rat uterine endometrium.
Akçalı, K. C., Khan, S., & Moulton, B. C. (1996) · Endocrinology · doi:10.1210/endo.137.7.8770938 · Cited by 65 · see citing works
CAUSES OF PERINATAL MORTALITY EXCESS IN PROLONGED GESTATIONS
Naeye, R. L. (1978) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a112641 · Cited by 64 · see citing works
The stillborn fetus: placental histologic examination in determining a cause.
Rayburn, W. F., Sander, C., Barr, M., & Rygiel, R. (1985) · PubMed · Cited by 60 · see citing works
False-positive apoptosis signal in mouse kidney and liver detected with TUNEL assay
Pulkkanen, K. J., Laukkanen, M. O., Naarala, J., & Ylä‐Herttuala, S. (2000) · APOPTOSIS · doi:10.1023/a:1009631424351 · Cited by 59 · see citing works
Gruslin, A., Qiu, Q., & Tsang, B. K. (2001) · Biology of Reproduction · doi:10.1095/biolreprod64.4.1264 · Cited by 58 · see citing works
"TO BE, OR NOT TO BE : THAT IS THE QUESTION"
勇, 齋. (1938) · 英文学研究 · doi:10.20759/elsjp.18.3_450 · Cited by 56 · see citing works
A morphometric study of maternal smoking on apoptosis in the syncytiotrophoblast
Marana, H. R. C., de Andrade, J. M., Martins, G. A., Silva, J. S., Sala, M. Á., & da Cunha, S. P. (1998) · International Journal of Gynecology & Obstetrics · doi:10.1016/s0020-7292(98)00014-9 · Cited by 42 · see citing works
BCL-2 expression in the human placenta and its correlation with fibrin deposits
Marzioni, D., Mühlhauser, J., Crescimanno, C., Baniţă, M., Pierleoni, C., & Castellucci, M. (1998) · Human Reproduction · doi:10.1093/humrep/13.6.1717 · Cited by 41 · see citing works
Dai, D., Moulton, B. C., & Ogle, T. F. (2000) · Biology of Reproduction · doi:10.1095/biolreprod63.1.188 · Cited by 39 · see citing works
Tomimatsu, T., Fukuda, H., Endo, M., Watanabe, N., Mu, J., Kohzuki, M., Fujii, E. Y., Kanzaki, T., & Murata, Y. (2001) · Neuroscience Letters · doi:10.1016/s0304-3940(01)02178-4 · Cited by 38 · see citing works
Self-citationHammer, A., & Dohr, G. (1999) · American Journal of Reproductive Immunology · doi:10.1111/j.1600-0897.1999.tb00471.x · Cited by 36 · see citing works
Immunohistochemical detection of apoptosis in the human term and post-term placenta.
Axt, R., Meyberg, R., Mink, D., Wasemann, C., Reitnauer, K., & Schmidt, W. (1999) · PubMed · Cited by 35 · see citing works
Toki, T. (1999) · Molecular Human Reproduction · doi:10.1093/molehr/5.3.246 · Cited by 31 · see citing works
Expression of Apoptosis in Placentae from Mice Lacking the Prostaglandin F Receptor
Mu, J., Kanzaki, T., Tomimatsu, T., Fukuda, H., Wasada, K., Fujii, E., Endoh, M., Kozuki, M., Murata, Y., Sugimoto, Y., et al. (2002) · Placenta · doi:10.1053/plac.2001.0759 · Cited by 26 · see citing works
Self-citationExpression of Apoptosis in Placentas from Mice Lacking the Prostaglandin F Receptor
穆, 俊. (2002) · Cited by 19 · see citing works
Apoptosis and Related Proteins during Parturition in Prostaglandin F Receptor-Deficient Mice
Mu, J., Kanzaki, T., Si, X., Tomimatsu, T., Fukuda, H., Fujii, E., Hosono, T., Murata, Y., Sugimoto, Y., & Ichikawa, A. (2002) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2002.6698 · Cited by 8 · see citing works
Self-citation
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Bech, B. H., Nohr, E. A., Vaeth, M., Henriksen, T. B., & Olsen, J. (2005) · American Journal of Epidemiology · doi:10.1093/aje/kwi317 · Cited by 202 · see citing works
Proteomic Analysis of the Extraembryonic Tissue from Cloned Porcine Embryos
Chae, J., Cho, S., Seo, J.-W., Yoon, T., Lee, K., Kim, J., Lee, K.-K., Han, Y., & Yu, K. (2006) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m500427-mcp200 · Cited by 55 · see citing works
Goeden, N., & Bonnin, A. (2012) · Nature Protocols · doi:10.1038/nprot.2012.144 · Cited by 44 · see citing works
Shaker, O. G., & Sadik, N. A. H. (2013) · Human & Experimental Toxicology · doi:10.1177/0960327112472998 · Cited by 43 · see citing works
Levy, O., Karako‐Lampert, S., Ben‐Asher, H. W., Zoccola, D., Pagès, G., & Ferrier‐Pagès, C. (2016) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2015.3025 · Cited by 35 · see citing works
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Jurisicova, A., Detmar, J., & Caniggia, I. (2005) · Birth Defects Research Part C Embryo Today Reviews · doi:10.1002/bdrc.20053 · Cited by 34 · see citing works
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Penha‐Gonçalves, C., Gozzelino, R., & de Moraes, L. V. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00155 · Cited by 16 · see citing works
Brown, J. L., Sones, J. L., Angulo, C. N., Abbott, K., Miller, A. D., Boehm, U., & Roberson, M. S. (2019) · Scientific Reports · doi:10.1038/s41598-019-45997-0 · Cited by 13 · see citing works
Shioji, M., Fukuda, H., Kanzaki, T., Wasada, K., Kanagawa, T., Shimoya, K., Mu, J., Sugimoto, Y., & Murata, Y. (2006) · Journal of obstetrics and gynaecology research · doi:10.1111/j.1447-0756.2006.00425.x · Cited by 13 · see citing works
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Güven, E. S. G., Okur, H., & Beksaç, M. S. (2008) · American Journal of Reproductive Immunology · doi:10.1111/j.1600-0897.2008.00583.x · Cited by 9 · see citing works
Prostanoid receptors (version 2019.5) in the IUPHAR/BPS Guide to Pharmacology Database
BREYER, R. M., Clapp, L. H., Coleman, R. A., Giembycz, M. A., Heinemann, Á., Hills, R., Jones, R. L., Narumiya, S., Norel, X., Pettipher, R., et al. (2019) · IUPHAR/BPS Guide to Pharmacology CITE · doi:10.2218/gtopdb/f58/2019.5 · Cited by 5 · see citing works
Self-citationHuai, J., Li, G., Li, L., Ma, J., & Yang, H.-X. (2020) · PubMed Central · Cited by 4 · see citing works
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Self-citationАртемьева, К. А., Степанова, И. И., Богданова, И. М., Boltovskaya, M. N., Yaglova, N. V., Obernikhin, S. S., & Ponomarenko, E. A. (2022) · Bulletin of Experimental Biology and Medicine · doi:10.1007/s10517-022-05474-7 · Cited by 3 · see citing works
Prostanoid receptors in GtoPdb v.2023.1
Clapp, L. H., Giembycz, M. A., Heinemann, Á., Jones, R. L., Narumiya, S., Norel, X., Sugimoto, Y., Woodward, D. F., & Yao, C. (2023) · IUPHAR/BPS Guide to Pharmacology CITE · doi:10.2218/gtopdb/f58/2023.1 · Cited by 3 · see citing works
Self-citationSiggers, R. H., Shirkey, T. W., Drew, M. D., Laarveld, B., & Kessel, A. G. V. (2008) · Canadian Journal of Animal Science · doi:10.4141/cjas07121 · Cited by 3 · see citing works
Ex vivo Perfusion of the Mouse Placenta for Maternal–Fetal Interaction Studies during Pregnancy
Goeden, N., & Bonnin, A. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-394445-0.00057-6 · Cited by 2 · see citing works
Shawer, H. M., Aiyelaagbe, E., Clowes, C., Lean, S. C., Lu, Y., Kadler, K. E., Kerby, A., Dilworth, M. R., Hentges, K. E., & Heazell, A. E. P. (2020) · PLoS ONE · doi:10.1371/journal.pone.0233007 · Cited by 1 · see citing works
Lo, T. K., Lau, W. L., & Leung, W. C. (2008) · International Journal of Gynecology & Obstetrics · doi:10.1016/j.ijgo.2008.03.009
The detection and role of human endogenous retrovirus K (HML-2) in rheumatoid arthritis
Freimanis, G. (2008) · Wolverhampton Intellectual Repository and E-Theses (University of Wolverhampton)
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Pratanu, L. (2023) · Women Health Care and Issues · doi:10.31579/2642-9756/153
Elmore, S. A., Cochran, R. Z., Ganta, C., Jensen, H., Lubeck, B. A., Mahler, B. W., Sabio, D. A., Stamper, G., & Bolon, B. N. (2026) · Toxicologic Pathology · doi:10.1177/01926233261436343
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- Authors
- Mu, J., Kanzaki, T., Si, X., Tomimatsu, T., Fukuda, H., Shioji, M., Murata, Y., Sugimoto, Y., & Ichikawa, A.
- Affiliations
- The University of Osaka (JP)
- Kyoto University (JP)
- Corresponding author
- Mu, Junwu
- Venue
- Biology of Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-06-01
- Volume
- 68
- Issue
- 6
- Pages
- 1968-1974
- ISSN
- 0006-3363 (ISSN-L)
- 1529-7268
- OpenAlex
- W1989324410
- Cited by
- 26
- References
- 52
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2020: 3 · 2019: 2 · 2016: 1 · 2014: 1 · 2013: 3 · 2012: 1
- FWCI
- 0.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biology of Reproduction (publishedVersion)
- PubMed (publishedVersion)
- BioOne Complete (BioOne) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- apoptosis, placenta, intrauterine fetal death, prostaglandin F receptor, syncytiotrophoblast, decidua, caspase-3, Bcl-2, Bax/Bcl-2 ratio, receptor-deficient mice, TUNEL staining
- MeSH terms
- Animals, Female, Fetal Death, Immunohistochemistry, Pregnancy, Pregnancy Proteins, Proteins, Proto-Oncogene Proteins, Receptors, Prostaglandin, Protein Biosynthesis, Blotting, Western, Dinoprost, Apoptosis, In Situ Hybridization, Mice, Knockout, Proto-Oncogene Proteins c-bcl-2, Genes, bcl-2, Caspases, In Situ Nick-End Labeling, bcl-2-Associated X Protein, Mice, Caspase 3
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