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 8 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 vs. control)
but was fully restored by voluntary wheel running (p < 0.05 vs.
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.