Trp53 deficient mice predisposed to preterm birth display region-specific lipid alterations at the embryo implantation site.
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.
Physical Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99352, USA.|Department of Chemistry-BMC, Uppsala University, Sweden.
Ingela
I
Lanekoff
Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Jeeyeon
J
Cha
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99352, USA.
Jennifer E
JE
Kyle
Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Sudhansu K
SK
Dey
Physical Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99352, USA.
Julia
J
Laskin
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99352, USA.
Kristin E
KE
Burnum-Johnson
D000818:Animals; D004075:Diglycerides / Q000378:metabolism; D010064:Embryo Implantation / Q000235:genetics* / Q000502:physiology*; D005260:Female; D016158:Genes, p53; D050356:Lipid Metabolism / Q000235:genetics*; D000076222:Mechanistic Target of Rapamycin Complex 1 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000378:metabolism; D011247:Pregnancy; D021241:Spectrometry, Mass, Electrospray Ionization; D014599:Uterus / Q000378:metabolism*
D004075:Diglycerides; D010713:Phosphatidylcholines; D000076222:Mechanistic Target of Rapamycin Complex 1