title: Activation of peroxisome proliferator activator receptor delta in mouse impacts lipid composition and placental development at early stage of gestation.
abstract: Peroxisome proliferator-activated receptor delta (Ppard) activation has been implicated in regulating a multitude of biological processes in placental development. In this study, we employed the UPLC-ESI-TOFMS approach to investigate the metabolic traits in placenta from GW501516-treated mice at Embryonic Day 10.5. By analyzing the mass spectrum data, ions with the most significant differences between control and GW501516-treated groups were identified. Among these metabolites, the fatty acids, phospholipids, and sterol lipids were dramatically increased. Ingenuity Pathway Analysis (IPA) showed that phosphatidylethanolamine biosynthesis and glycolysis were the top two altered metabolic pathways involved in carbohydrate metabolism, energy production, and lipid metabolism. Subsequent immunoblotting experiments provided evidence for positive correlation of PPARD level and AKT and ERK signaling pathways upon GW501516 treatment. Furthermore, the stimulation of GW501516 increased trophoblast cell fusion gene syncytin-A (Syna), but not syncytin-B (Synb), expression, suggesting a potential role of Ppard activation in promoting cytotrophoblast differentiation. Our results reveal that Ppard activation elicits dramatic changes of the metabolic activities in placenta, which is correlated to AKT and ERK signaling.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Obstetrics, Affiliated Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Ding
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Yiyu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Beijing Agriculture Institution, Beijing, China.
authors.forename: Lun
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Obstetrics, Affiliated Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Obstetrics, Affiliated Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Qu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Oncology, Affiliated Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China drrongshen@gmail.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Shen
mesh_terms: D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D055442:Metabolome / Q000187:drug effects; D008822:Mice, Transgenic; D000072079:Patched Receptors; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010920:Placenta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010929:Placentation / Q000187:drug effects; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology
chemical_list: C425931:GW 501516; D000072079:Patched Receptors; D010714:Phosphatidylethanolamines; C091778:Ppard protein, mouse; D011257:Pregnancy Proteins; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; C497514:syncytin-A protein, mouse; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt
keywords: Ppard; UPLC-ESI-TOFMS approach; metabolism; peroxisome proliferator activator receptor delta; placenta; pregnancy; signaling pathway