Heat stress (HS) affects female reproductive efficiency by disrupting redox homeostasis and activating inflammatory responses in the corpus luteum (CL), a metabolically active tissue essential for pregnancy maintenance. This study reveals the protective effect of resveratrol against HS-induced luteal injury in pregnant mice through the regulation of oxidative stress and cytokine–chemokine-mediated inflammatory and immune responses. The pregnant mice were divided into three groups: control, HS, and resveratrol +HS. Heat stress was applied at 40 ± 0.5 °C for 7 days, with resveratrol (10 mg/kg) given orally 2 h before exposure to HS. The results showed that heat exposure reduced serum total superoxide dismutase activity and increased malondialdehyde level, causing significant disruption of luteal morphology with cellular disorder and vacuolization, which was partially overcome by resveratrol pretreatment. Transcriptomic profiling showed that HS induced a strong immunological and inflammatory response, involving cytokine–cytokine receptor interaction and chemokine signaling. Resveratrol significantly attenuated HS-induced transcriptional changes. The RT-qPCR results showed that HS increased chemokine ligands (Ccl11, Cxcl13, Tslp) and cytokine receptors (Ccr3, Ccr4, Ccr5), which were suppressed by resveratrol. The chemokine-based inflammatory module is one of the most important regulatory properties of the HS response, according to the network analysis. Stable binding of resveratrol with major chemokine receptors was supported by molecular docking and molecular dynamics simulations. Collectively, HS induces oxidative, structural, and inflammatory alterations in luteal tissue, while resveratrol attenuates these changes by being associated with improved antioxidant status and suppression of cytokine–chemokine-mediated responses.
Tariq et al. (Tue,) studied this question.