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Sci Rep. 2016 Sep 13;6:33023. doi: 10.1038/srep33023.

Trp53 deficient mice predisposed to preterm birth display region-specific lipid alterations at the embryo implantation site.

Author information

1
Physical Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99352, USA.
2
Department of Chemistry-BMC, Uppsala University, Sweden.
3
Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
4
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99352, USA.

Abstract

Here we demonstrate that conditional deletion of mouse uterine Trp53 (p53(d/d)), molecularly linked to mTORC1 activation and causally linked to premature uterine senescence and preterm birth, results in aberrant lipid signatures within the heterogeneous cell types of embryo implantation sites on day 8 of pregnancy. In situ nanospray desorption electrospray ionization mass spectrometry imaging (nano-DESI MSI) was used to characterize the molecular speciation of free fatty acids, monoacylglycerol species, unmodified and oxidized phosphatidylcholine (PC/Ox-PC), and diacylglycerol (DG) species within implantation sites of p53(d/d) mice and floxed littermates. Implantation sites from p53(d/d) mice exhibited distinct spatially resolved changes demonstrating accumulation of DG species, depletion of Ox-PC species, and increase in species with more unsaturated acyl chains, including arachidonic and docosahexaenoic acid. Understanding abnormal changes in the abundance and localization of individual lipid species early in the progression to premature birth is an important step toward discovering novel targets for treatments and diagnosis.

PMID:
27620843
PMCID:
PMC5020559
DOI:
10.1038/srep33023
[Indexed for MEDLINE]
Free PMC Article

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