Paternal physical inactivity alters offspring sex ratio and is associated with heritable impairments in reproductive success in rats

Paternal lifestyle factors are increasingly recognized as determinants of offspring health, yet the effects of physical inactivity on reproduction remain unclear. Here, we demonstrated that paternal physical inactivity caused a bias in offspring sex ratio and reduced fertility across generations in rats. Male rats subjected to eight weeks of restricted activity produced offspring with a female-biased sex ratio (female : male = 39 : 16; p = 0.011; odds ratio = 2.84) compared with controls (24 : 28). Sperm motility was markedly reduced in inactive fathers (p < 0.001 versus control) but was fully restored by voluntary wheel running (p < 0.05 versus inactive), indicating reversibility of this functional impairment. Cross-mating of first-filial-generation (F1) rats of inactive paternal origin revealed that females derived from inactive fathers exhibited lower pregnancy rates and smaller litter size, whereas F1 males displayed normal fertility. Remarkably, intercrosses between F1 males and females of inactive paternal origin produced no viable offspring surviving to weaning age. Although the sample size was limited, this outcome suggests a heritable impairment in reproductive success. These findings identify paternal physical inactivity as an environmental factor influencing offspring sex ratio and reproductive success across generations; however, studies with larger mating cohorts are needed to confirm this transgenerational phenotype.