# PPARγ activation rescues oxidative stress-induced embryonic arrest by suppressing Wnt/β-catenin signaling via GSK3β upregulation

## 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.

## Key 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 guardian of embryonic redox and metabolic homeostasis, and propose PPARγ agonism as a potential strategy to improve ART outcomes by counteracting oxidative injury.

•PPARγ activation rescues oxidative stress-induced embryonic arrest•PPARγ upregulates GSK3β to suppress aberrant Wnt/β-catenin signaling•PPARγ agonist GW1929 restores redox/metabolic homeostasis in embryos

PPARγ activation rescues oxidative stress-induced embryonic arrest

PPARγ upregulates GSK3β to suppress aberrant Wnt/β-catenin signaling

PPARγ agonist GW1929 restores redox/metabolic homeostasis in embryos

Biological sciences; Developmental genetics; Developmental biology