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p53 regulates maternal reproduction through LIF.
- Source :
-
Nature [Nature] 2007 Nov 29; Vol. 450 (7170), pp. 721-4. - Publication Year :
- 2007
-
Abstract
- Extensive studies have shown that p53 is important in tumour prevention. However, little is known about its normal physiological function. Here we show that p53 is important in reproduction, in a gender-specific manner. Significant decreases in embryonic implantation, pregnancy rate and litter size were observed in matings with p53-/- female mice but not with p53-/- male mice. The gene encoding leukaemia inhibitory factor (LIF), a cytokine critical for implantation, was identified as a p53-regulated gene that functions as the downstream mediator of this effect. p53 can regulate both basal and inducible transcription of LIF. Loss of p53 decreased both the level and function of LIF in uteri. Lower LIF levels were observed in the uteri of p53-/- mice than in those of p53+/+ mice, particularly at day 4 of pregnancy, when transiently induced high levels of LIF were crucial for embryonic implantation. This observation probably accounts for the impaired implantation of embryos in p53-/- female mice. Administration of LIF to pregnant p53-/- mice restored maternal reproduction by improving implantation. These results demonstrate a function for p53 in maternal reproduction through the regulation of LIF. Evidence is accumulating that p53 may have a similar function in humans.
- Subjects :
- Animals
Consensus Sequence genetics
Embryo Implantation genetics
Female
Gene Expression Regulation
Genes, p53 genetics
Genotype
Leukemia Inhibitory Factor deficiency
Leukemia Inhibitory Factor genetics
Litter Size genetics
Litter Size physiology
Male
Mice
Pregnancy genetics
Pregnancy physiology
Reproduction genetics
Tumor Suppressor Protein p53 deficiency
Tumor Suppressor Protein p53 genetics
Uterus metabolism
Leukemia Inhibitory Factor metabolism
Mothers
Reproduction physiology
Tumor Suppressor Protein p53 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 450
- Issue :
- 7170
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 18046411
- Full Text :
- https://doi.org/10.1038/nature05993