Maternal aging reduces female fecundity and alters offspring phenotype in a sex-specific manner

Context The age of childbearing in women has increased, with more babies born to women over 30years old than to those in their 20s. However, increasing maternal age is associated with a range of pregnancy and perinatal complications, such as reduced chance of conception, and higher risk of miscarriage or fetal death. Further, epidemiological studies indicate that advanced maternal age is also linked to a higher incidence of metabolic and neurodevelopmental disorders in offspring, such as Type 1 diabetes and autism spectrum disorder (ASD). Aims Mature female mice recapitulate many of the fertility characteristics seen in older women, such as reduced egg number and quality, providing a robust experimental model. This study examined fertility and offspring phenotypes in female mice at the onset of reproductive aging. Methods Firstly, fecundity in mice was measured from 3 to 18months of age. Secondly, reproductive outcomes in aged female mice (12months old) were compared to those of young females (3months of age). Growth of the offspring was assessed, as well as metabolism, behaviour, and immune function in adulthood. Key results Female aging reduced pregnancy rate, litter size and pup survival to weaning. Maternal age did not affect adult offspring immune function; however, female offspring had higher body weights, and male littermates presented dysregulated glucose tolerance and hyperactivity. Conclusions Maternal age affects offspring survival and health in a sex-specific manner. Implications These findings expand our understanding of maternal programming of offspring health, particularly the effects of increased age at pregnancy.