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However, the underlying etiology remains unclear. Here, it is reported that the placentas of women with pregnancies complicated with FGR exhibit peroxisome proliferator\u2010activated receptor \u03b3 (PPAR\u03b3) inactivation. In mice, trophoblast\u2010specific ablation of murine PPAR\u03b3 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 PPAR\u03b3 proteins. Moreover, nanoparticle\u2010mediated placenta\u2010specific delivery of rosiglitazone (RGZ) significantly rescues adipogenesis defects in an FGR\u2010induced mouse model. In summary, the placenta is a major reservoir of PPAR\u03b3. An insufficient supply of placental PPAR\u03b3 to fetal preadipocytes via exosomes during late gestation is a major mechanism underlying FGR. Preclinically, placenta\u2010targeted RGZ administration can be a promising interventional therapy for FGR and\/or defective intrauterine fat development.<\/jats:p>","DOI":"10.1002\/advs.202404983","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T10:11:58Z","timestamp":1739527918000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Placenta Regulates Intrauterine Fetal Growth via Exosomal PPAR\u03b3"],"prefix":"10.1002","volume":"12","author":[{"given":"Xiaofang","family":"Luo","sequence":"first","affiliation":[{"name":"Reproductive Medicine Center The First Affiliated Hospital of Chongqing Medical University  Chongqing 400016 China"},{"name":"State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality The First Affiliated Hospital of Chongqing Medical University  Chongqing 400016 China"},{"name":"Ministry of Education International Collaborative 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