Advanced Paternal Age Affects Sperm Count and Anogenital Distance in Mouse Offspring

In Western society, couples increasingly delay parenthood until later in life. Overall, studies have focused on the reproductive performance of older parents or the impact of advanced maternal age on pregnancy outcomes, but few studies have examined how advanced paternal age (APA) affects offspring health. The aim of this study was to investigate the impact of increasing paternal age on offspring reproductive performance and long-term metabolic health in a mouse model. Here, the same adult B6D2F1/J male mice were mated at 4, 12, and 18 months of age with 6- to 10-week-old naturally cycling CF1 females to generate 3 offspring cohorts conceived at increasing paternal ages PA4, PA12, and PA18. The offspring resulting from mating the same fathers at different ages (n = 20 per age; 10 males and 10 females) were maintained up to 20 weeks of age and morphometric parameters, growth curve, and glucose tolerance were measured. We found that increasing paternal age was associated with a trend toward longer time to conception. Litter sizes were not significantly different. Reassuringly, metabolic parameters and growth curve were not different in the 3 cohorts of offspring. Most importantly, increased paternal age (PA4 vs PA18) was associated with a statistically significant decrease in sperm concentration, sperm motility, and anogenital distance in offspring. These changes raise concerns about the potential impact of APA on the reproductive fitness in males of the next generation.