Impact of maternal obesity on placental transcriptome and morphology associated with fetal growth restriction in mice
Autor: | Thomas J. Ashmore, Elena Loche, Laura C. Kusinski, Maria das Graças Tavares do Carmo, Phoebe Wilsmore, Denise S. Fernandez-Twinn, Lucas Carminatti Pantaleão, Heather L. Blackmore, Susan E. Ozanne, Daniela de Barros Mucci |
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Přispěvatelé: | Fernandez-Twinn, Denise S. [0000-0003-2610-277X], Apollo - University of Cambridge Repository, Fernandez-Twinn, Denise S [0000-0003-2610-277X] |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male Offspring Endocrinology Diabetes and Metabolism Birth weight Placenta Medicine (miscellaneous) Biology 38/91 Andrology Transcriptome Obesity Maternal 03 medical and health sciences Mice 0302 clinical medicine 631/1647/767/1424 Animal disease models Pregnancy medicine Animals Obesity 101/1 Fetus 030219 obstetrics & reproductive medicine Nutrition and Dietetics PDGFB Fetal Growth Retardation article Phenotype Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure In utero embryonic structures 38/77 692/699/1702/393 64/60 Female |
Zdroj: | International Journal of Obesity (2005) |
DOI: | 10.17863/cam.49249 |
Popis: | Background In utero exposure to obesity is consistently associated with increased risk of metabolic disease, obesity and cardiovascular dysfunction in later life despite the divergence of birth weight outcomes. The placenta plays a critical role in offspring development and long-term health, as it mediates the crosstalk between the maternal and fetal environments. However, its phenotypic and molecular modifications in the context of maternal obesity associated with fetal growth restriction (FGR) remain poorly understood. Methods Using a mouse model of maternal diet-induced obesity, we investigated changes in the placental transcriptome through RNA sequencing (RNA-seq) and Ingenuity Pathway Analysis (IPA) at embryonic day (E) 19. The most differentially expressed genes (FDR Results RNA-seq and IPA analyses revealed differential expression of transcripts and pathway interactions related to placental vascular development and tissue morphology in obese placentae at term, including downregulation of Muc15, Cnn1, and Acta2. Pdgfb, which is implicated in labyrinthine layer development, was downregulated in obese placentae at E13. This was consistent with the morphological evidence of reduced labyrinth zone (LZ) size, as well as lower fetal weight at both timepoints irrespective of offspring sex. Conclusions Maternal obesity results in abnormal placental LZ development and impaired vascularization, which may mediate the observed FGR through reduced transfer of nutrients across the placenta. |
Databáze: | OpenAIRE |
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