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Moderate maternal nutrient reduction in pregnancy alters fatty acid oxidation and RNA splicing in the nonhuman primate fetal liver.

ABSTRACT: Fetal liver tissue collected from a nonhuman primate (NHP) baboon model of maternal nutrient reduction (MNR) at four gestational time points (90, 120, 140, and 165 days gestation [dG], term in the baboon is ∼185 dG) was used to quantify MNR effects on the fetal liver transcriptome. 28 transcripts demonstrated different expression patterns between MNR and control livers during the second half of gestation, a developmental period when the fetus undergoes rapid weight gain and fat accumulation. Differentially expressed transcripts were enriched for fatty acid oxidation and RNA splicing-related pathways. Increased RNA splicing activity in MNR was reflected in greater abundances of transcript splice variant isoforms in the MNR group. It can be hypothesized that the increase in splice variants is deployed in an effort to adapt to the poor in utero environment and ensure near-normal development and energy metabolism. This study is the first to study developmental programming across four critical gestational stages during primate fetal liver development and reveals a potentially novel cellular response mechanism mediating fetal programming in response to MNR.

SUBMITTER: Zimmerman KD

PROVIDER: S-EPMC10202844 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Moderate maternal nutrient reduction in pregnancy alters fatty acid oxidation and RNA splicing in the nonhuman primate fetal liver.

Zimmerman Kip D KD Chan Jeannie J Glenn Jeremy P JP Birnbaum Shifra S Li Cun C Nathanielsz Peter W PW Olivier Michael M Cox Laura A LA

Journal of developmental origins of health and disease 20230316 3

Fetal liver tissue collected from a nonhuman primate (NHP) baboon model of maternal nutrient reduction (MNR) at four gestational time points (90, 120, 140, and 165 days gestation [dG], term in the baboon is ∼185 dG) was used to quantify MNR effects on the fetal liver transcriptome. 28 transcripts demonstrated different expression patterns between MNR and control livers during the second half of gestation, a developmental period when the fetus undergoes rapid weight gain and fat accumulation. Dif ...[more]

PMID: 36924159

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Project description:Little is known about the repertoire of nonhuman primate kidney genes expressed throughout development. The present work establishes an understanding of the primate renal transcriptome at different stages of fetal development and defines the framework of gene expression in the context of renal maturation, which provides a basis for identifying deviations in transcriptome expression resulting from suboptimal conditions during renal development. The baboon kidney transcriptome was characterized at 60 days gestation (DG), 90DG, 125DG, 160DG and adulthood (6-12 years) using human genome arrays to identify differential gene expression in the context of biological pathways and hierarchical clusters. Whole genome expression profiling showed 11,331 genes that were expressed during kidney development, 4,698 of which were differentially expressed among the developmental time points. Pathway analysis indicated activation of annotated pathways previously reported to be important to kidney development and pathways not reported as relevant to kidney development. QRT-PCR for genes central to these pathways validated expression profiles and revealed differences between males and females at specific times in gestation. Hierarchical clustering indicated that two clusters best fit the data, one containing genes that increased in expression from 60DG to adult and one that decreased. Cluster analysis also revealed gene splice variants with discordant expression profiles during development. For example, SMAD4, which is central to Wnt signaling, TGF-β signaling and cell cycle, showed up-regulation of the full-length splice variant during development and down-regulation of a shorter variant that is missing DNA binding and protein heterotrimerization domains suggesting decreased inhibition of cell proliferation, which may impact renal cell number and maturation. This study provides the first detailed genetic analysis of the developing primate kidney, and our findings of discordant expression of gene splice variants suggest that gene arrays likely provide a simplified view and demonstrate the need to study the fetal renal proteome.

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Dataset Information

Moderate maternal nutrient reduction in pregnancy alters fatty acid oxidation and RNA splicing in the nonhuman primate fetal liver.

Publications

Moderate maternal nutrient reduction in pregnancy alters fatty acid oxidation and RNA splicing in the nonhuman primate fetal liver.

Similar Datasets

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