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
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:
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