Abstract
Background
Peroxisomal proliferator-activated receptors (PPARs) and microRNAs (miRNAs) play important roles in the development of fetuses, whereas expression changes of PPARs and three miRNAs (miR-17, miR-27b and miR-34a) and whether these miRNAs regulate PPARs in non-GDM macrosomia placenta is unclear.
Methods
A case–control study was performed to collect information and placental tissues on mothers and newborns of non-GDM macrosomia and normal-birth-weight infants. In vitro HTR8-SVneo cellular model was used to detect the effects of miRNAs on PPARs expression. Quantitative real-time PCR (qRT-PCR) and western blot was applied to examine the expression levels of PPARs, miR-17, miR-27b, and miR-34a in placental tissues and cells.
Results
The PPARα/γ mRNA and protein levels were significantly up-regulated and miR-27b was down-regulated in the placenta of macrosomia group compared with in the control group, while no difference was observed in PPARβ, miR-17, and miR-34a. After adjusting for confounding factors, low miR-27b and high PPARα/γ mRNA expression still increased the risk of macrosomia. The PPARα/γ protein levels presented a corresponding decrease or increase when cells were transfected with miR-27b mimic or inhibitor.
Conclusions
Placental PPARα/γ and miR-27b expression were associated with non-GDM macrosomia and miR-27b probably promotes the occurrence of non-GDM macrosomia by regulating PPARα/γ protein.
Impact
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Low miR-27b and high PPARα/γ mRNA expression in the placenta were associated with higher risk of macrosomia.
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In vitro HTR8-SVneo cell experiment supported that miR-27b could negatively regulate the expression of PPARα and PPARγ protein.
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MiR-27b was probably involved in non-GDM macrosomia through negative regulation of PPARα/γ protein.
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Data availability
The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
The authors are thankful to the participants for cooperation and medical staff for their work on information collection.
Funding
This work was funded by Zhejiang Public Welfare Technology Research Program/Social Development (project no.LGF20H260012) and Zhejiang Medical and Health Project (2018KY121).
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X.-J.Y. conceived and designed the study. L.-F.N. conducted experiments and drafted the manuscript. Y.H. conducted experiments and collected the data. Y.-H.W. collected the placenta tissue samples. S.-S.W. and X.-J.L. collected the data and conducted the statistical analyses. H.-T.Y. critically revised the manuscript.
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Ni, LF., Han, Y., Wang, SS. et al. Association of placental PPARα/γ and miR-27b expression with macrosomia in healthy pregnancy. Pediatr Res 93, 267–273 (2023). https://doi.org/10.1038/s41390-022-02072-1
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DOI: https://doi.org/10.1038/s41390-022-02072-1
