Paternal Exposure to PM_2.5 Programs Offspring's Energy Homeostasis

Considerable studies show that maternal exposure to ambient fine particulate matter (PM_2.5) programs offspring's susceptibility to obesity. However, few studies have investigated the effect of paternal PM_2.5 exposure on offspring's energy homeostasis. This study thus tested whether paternal PM_2.5 exposure programs offspring's energy homeostasis. Male C57Bl/6J mice were exposed to filtered air or concentrated ambient PM_2.5 (CAP) for 12 weeks and then mated with normal female C57Bl/6J mice. The offspring were assessed for growth trajectories, food intakes, and body compositions, and the sperm miRNAs of those sires were profiled by microarray. Zygotic injection was used to test whether the miRNA identified by the microarray mediates the impact of paternal PM_2.5 exposure on offspring's energy homeostasis. Paternal CAP exposure resulted in significant hypophagia and weight loss in male, but not female, offspring. The weight loss of male offspring was accompanied by decreases in the liver and kidney masses and paradoxically an increase in the adipose mass. Without further exposure to CAP, this programming was three-generationally transmitted along the paternal line. The sperm miRNA profiling revealed that mmu-mir6909-5p was the sole differentially expressed sperm miRNA due to PM_2.5 exposure, and zygotic injection of mmu-mir6909-5p mimicked all the effects of paternal PM_2.5 exposure on offspring's energy homeostasis. Paternal PM_2.5 exposure programs offspring's energy homeostasis through increasing paternal sperm mmu-mir6909-5p.