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dc.contributor.author Dey, Sudhansu K.
dc.contributor.author Bradshaw, Heather B.
dc.contributor.author Xie, Huirong
dc.contributor.author Tranguch, Susanne
dc.contributor.author Daikoku, Takiko
dc.contributor.author Hirota, Yasushi
dc.date.accessioned 2012-03-02T21:49:35Z
dc.date.available 2012-03-02T21:49:35Z
dc.date.issued 2010-03
dc.identifier.citation Hirota Y, Daikoku T, Tranguch S, Xie H, Bradshaw HB, Dey SK. p53 deficiency confers premature uterine senescence and promotes preterm birth. J Clin Invest. 2010 Mar 1;120(3):803-15 en
dc.identifier.uri http://www.jci.org/articles/view/40051 en
dc.identifier.uri http://hdl.handle.net/2022/14216
dc.description.abstract Many signaling pathways that contribute to tumorigenesis are also functional in pregnancy, although they are dysregulated in the former and tightly regulated in the latter. Transformation-related protein 53 (Trp53), which encodes p53, is a tumor suppressor gene whose mutation is strongly associated with cancer. However, its role in normal physiological processes, including female reproduction, is poorly understood. Mice that have a constitutive deletion of Trp53 exhibit widespread development of carcinogenesis at early reproductive ages, compromised spermatogenesis, and fetal exencephaly, rendering them less amenable to studying the role of p53 in reproduction. To overcome this obstacle, we generated mice that harbor a conditional deletion of uterine Trp53 and examined pregnancy outcome in females with this genotype. These mice had normal ovulation, fertilization, and implantation; however, postimplantation uterine decidual cells showed terminal differentiation and senescence-associated growth restriction with increased levels of phosphorylated Akt and p21, factors that are both known to participate in these processes in other systems. Strikingly, uterine deletion of Trp53 increased the incidence of preterm birth, a condition that was corrected by oral administration of the selective COX2 inhibitor celecoxib. We further generated evidence to suggest that deletion of uterine Trp53 induces preterm birth through a COX2/PGF synthase/PGF2α pathway. Taken together, our observations underscore what we believe to be a new critical role of uterine p53 in parturition. en
dc.language.iso en_US en
dc.publisher American Society for Clinical Investigation en
dc.rights Copyright © 2010, American Society for Clinical Investigation en
dc.title Uterine-specific p53 deficiency confers premature uterine senescence and promotes preterm birth in mice en
dc.type Article en


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