Biological sex impacts oxidative stress in skeletal muscle in a porcine heat stress model.

Oxidative stress contributes to heat stress (HS)-mediated alterations in skeletal muscle; however, the extent to which biological sex mediates oxidative stress during HS remains unknown. We hypothesized muscle from males would be more resistant to oxidative stress caused by HS than muscle from females. To address this, male and female pigs were housed in thermoneutral conditions (TN; 20.8 ± 1.6 °C; 62.0 ± 4.7% relative humidity; n = 8/sex) or subjected to HS (39.4 ± 0.6 °C; 33.7 ± 6.3% relative humidity) for 1 (HS1; n = 8/sex) or 7 days (HS7; n = 8/sex) followed by collection of the oxidative portion of the semitendinosus. While HS increased muscle temperature, by 7 d, muscle from heat-stressed females was cooler than muscle from heat-stressed males (0.3 °C; p<0.05). Relative protein abundance of 4-HNE-modified proteins increased in HS1 females compared to TN (p=0.05). Further, MDA-modified proteins and 8-OHdG concentration, a DNA damage marker, was increased in HS7 females compared to TN females (p=0.05). Enzymatic activities of catalase and SOD remained similar between groups; however, GPX activity decreased in HS7 females compared to TN and HS1 females (p≤0.03) and HS7 males (p=0.02). Notably, HS increased skeletal muscle Ca2+ deposition (p=0.05) and was greater in HS1 females compared to TN females (p<0.05). Heat stress increased SERCA2a protein abundance (p<0.01); however, Ca2+ ATPase activity remained similar between groups. Overall, despite having lower muscle temperature, muscle from heat-stressed females had increased markers of oxidative stress and calcium deposition than muscle from males following identical environmental exposure.