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

Abstract

Here we demonstrate that conditional deletion of mouse uterine Trp53 (p53d/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, monoacylglycerols, unmodified and oxidized phosphatidylcholine (PC/Ox-PC), and diacylglycerol (DG) species within implantation sites of p53d/d mice and floxed littermates. Implantation sites from p53d/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 important for discovering novel targets for treatments and diagnosis.

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)
Sponsoring Org.:
USDOE
OSTI Identifier:
1340811
Report Number(s):
PNNL-SA-116850
Journal ID: ISSN 2045-2322; 44679
DOE Contract Number:
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Scientific Reports; Journal Volume: 6
Country of Publication:
United States
Language:
English
Subject:
Nano-DESI mass spectrometry imaging; p53; preterm birth; Environmental Molecular Sciences Laboratory

Citation Formats

Lanekoff, Ingela, Cha, Jeeyeon, Kyle, Jennifer E., Dey, Sudhansu K., Laskin, Julia, and Burnum-Johnson, Kristin E. Trp53 deficient mice predisposed to preterm birth display region-specific lipid alterations at the embryo implantation site. United States: N. p., 2016. Web. doi:10.1038/srep33023.
Lanekoff, Ingela, Cha, Jeeyeon, Kyle, Jennifer E., Dey, Sudhansu K., Laskin, Julia, & Burnum-Johnson, Kristin E. Trp53 deficient mice predisposed to preterm birth display region-specific lipid alterations at the embryo implantation site. United States. doi:10.1038/srep33023.
Lanekoff, Ingela, Cha, Jeeyeon, Kyle, Jennifer E., Dey, Sudhansu K., Laskin, Julia, and Burnum-Johnson, Kristin E. Tue . "Trp53 deficient mice predisposed to preterm birth display region-specific lipid alterations at the embryo implantation site". United States. doi:10.1038/srep33023.
@article{osti_1340811,
title = {Trp53 deficient mice predisposed to preterm birth display region-specific lipid alterations at the embryo implantation site},
author = {Lanekoff, Ingela and Cha, Jeeyeon and Kyle, Jennifer E. and Dey, Sudhansu K. and Laskin, Julia and Burnum-Johnson, Kristin E.},
abstractNote = {Here we demonstrate that conditional deletion of mouse uterine Trp53 (p53d/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, monoacylglycerols, unmodified and oxidized phosphatidylcholine (PC/Ox-PC), and diacylglycerol (DG) species within implantation sites of p53d/d mice and floxed littermates. Implantation sites from p53d/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 important for discovering novel targets for treatments and diagnosis.},
doi = {10.1038/srep33023},
journal = {Scientific Reports},
number = ,
volume = 6,
place = {United States},
year = {Tue Sep 13 00:00:00 EDT 2016},
month = {Tue Sep 13 00:00:00 EDT 2016}
}