PPARγ activation rescues oxidative stress-induced embryonic arrest by suppressing Wnt/β-catenin signaling via GSK3β upregulation
Lihong Liu, Siyao Ha, Hui Chen, MingQing Li, Zhiling Li
TL;DR
PPARγ activation helps embryos survive oxidative stress by regulating GSK3β and Wnt/β-catenin signaling, improving ART outcomes.
Contribution
Identifies PPARγ as a key regulator of embryonic redox and metabolic homeostasis during oxidative stress.
Findings
PPARγ activation rescues oxidative stress-induced embryonic arrest by scavenging ROS and restoring mitochondrial function.
PPARγ upregulates GSK3β, which suppresses aberrant Wnt/β-catenin signaling in stressed embryos.
The PPARγ agonist GW1929 restores redox and metabolic homeostasis in embryos exposed to oxidative stress.
Abstract
Excessive reactive oxygen species (ROS) during assisted reproductive technology (ART) impairs embryonic development, yet the intrinsic molecular mechanisms remain inadequately understood. Through transcriptomic profiling (Drug-seq) of oxidatively stressed mouse embryos, we identified peroxisome proliferator-activated receptor gamma (PPARγ) as a critical regulator whose essential upregulation during zygotic genome activation (ZGA) is suppressed. Functional studies demonstrated that the pharmacological activation of PPARγ via the agonist GW1929 robustly rescued developmental arrest by scavenging ROS, restoring mitochondrial function, and maintaining metabolic homeostasis. Mechanistically, we demonstrate that PPARγ activation transcriptionally upregulates GSK3β, which in turn suppresses oxidative stress-induced aberrant Wnt/β-catenin signaling. Our findings establish PPARγ as a central…
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Taxonomy
TopicsPeroxisome Proliferator-Activated Receptors · NF-κB Signaling Pathways · Aldose Reductase and Taurine