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Trp53 deficient mice predisposed to preterm birth display region-specific lipid alterations at the embryo implantation site
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Pacific Northwest Natl Lab, Div Phys Sci, Richland, WA 99352 USA..
Cincinnati Childrens Hosp Med Ctr, Div Reprod Sci, Cincinnati, OH 45229 USA.;Vanderbilt Univ, Dept Med, 221 Kirkland Hall, Nashville, TN 37235 USA..
Pacific Northwest Natl Lab, Biol Sci Div, Richland, WA 99352 USA..
Cincinnati Childrens Hosp Med Ctr, Div Reprod Sci, Cincinnati, OH 45229 USA..
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2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 33023Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2016. Vol. 6, 33023
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:uu:diva-304147DOI: 10.1038/srep33023ISI: 000382917700002PubMedID: 27620843OAI: oai:DiVA.org:uu-304147DiVA: diva2:1014982
Funder
NIH (National Institute of Health), HD068524 DA06668Swedish Research Council, 621-2013-4231Swedish Foundation for Strategic Research , ICA-6
Available from: 2016-10-03 Created: 2016-10-03 Last updated: 2017-11-30Bibliographically approved

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