The placenta regulates intrauterine fetal growth via exosomal PPARγ

Luo, Xiaofang, Huang, Biao, Xu, Ping, Wang, Hao, Zhang, Baozhen, Lin, Li, Liao, Jiujiang, Hu, Mingyu, Liu, Xiyao, Huang, Jiayu, Fu, Yong, Kilby, Mark D., Kellems, Rodney E., Fan, Xiujun, Xia, Yang, Baker, Philip N., Qi, Hongbo and Tong, Chao (2025) The placenta regulates intrauterine fetal growth via exosomal PPARγ. Advanced Science, 12 (15). ISSN 2198-3844

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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.

Item Type:	Article
Additional Information:	Data Availability Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request. Funding information: This work was supported by the National Key R&D Program of China (2022YFC2702400) and the National Natural Science Foundation of China (U23A20406, U21A20346, 81771613, 82071675, 82001581, 82171662, 82101711).
Uncontrolled Keywords:	adipogenesis,exosomes,fetal growth restriction,placentas,pparγ,trophoblasts,medicine (miscellaneous),chemical engineering(all),materials science(all),biochemistry, genetics and molecular biology (miscellaneous),engineering(all),physics and astronomy(all) ,/dk/atira/pure/subjectarea/asjc/2700/2701
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	08 May 2025 15:30
Last Modified:	08 May 2025 15:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/99228
DOI:	10.1002/advs.202404983

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