Faculty, Staff and Student Publications
Language
English
Publication Date
4-1-2025
Journal
Advanced Science
DOI
10.1002/advs.202404983
PMID
39951006
PMCID
PMC12005745
PubMedCentral® Posted Date
2-14-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Abnormal adipogenesis is a major contributor to fetal growth restriction (FGR) and its associated complications. However, the underlying etiology remains unclear. Here, it is reported that the placentas of women with pregnancies complicated with FGR exhibit peroxisome proliferator-activated receptor γ (PPARγ) inactivation. In mice, trophoblast-specific ablation of murine PPARγ reproduces the phenotype of human fetuses with FGR and defective adipogenesis. Coculture of trophoblasts with preadipocytes significantly improves preadipocyte commitment and differentiation and increases the transcription of a series of adipogenic genes via intercellular transfer of exosomal PPARγ proteins. Moreover, nanoparticle-mediated placenta-specific delivery of rosiglitazone (RGZ) significantly rescues adipogenesis defects in an FGR-induced mouse model. In summary, the placenta is a major reservoir of PPARγ. An insufficient supply of placental PPARγ to fetal preadipocytes via exosomes during late gestation is a major mechanism underlying FGR. Preclinically, placenta-targeted RGZ administration can be a promising interventional therapy for FGR and/or defective intrauterine fat development.
Keywords
Female, PPAR gamma, Pregnancy, Placenta, Animals, Mice, Humans, Fetal Growth Retardation, Exosomes, Fetal Development, Adipogenesis, Trophoblasts, Rosiglitazone, Adipocytes
Published Open-Access
yes
Recommended Citation
Luo, Xiaofang; Huang, Biao; Xu, Ping; et al., "The Placenta Regulates Intrauterine Fetal Growth via Exosomal PPARγ" (2025). Faculty, Staff and Student Publications. 2835.
https://digitalcommons.library.tmc.edu/uthmed_docs/2835