Increased locomotor activity does not mitigate the effects of advanced maternal age in a mouse model

Introduction: Advanced maternal age (AMA) increases the risk of pregnancy complications, in part due to impaired placentation. While exercise during pregnancy can improve outcomes, its potential to mitigate the effects of AMA has not been investigated. We evaluated the impact of exercise in a mouse model of AMA. Methods: Females were paired with males at 9 or 34 weeks of age, with one group of aged females having access to running wheels four weeks prior to and during pregnancy. Pregnant females (N = 19 per group) were collected at gestational day (GD) 11.5. Placentas were collected for RNA sequencing (N = 17-20 per group). Results: Aged females without access to running wheels had heavier fat depots, while those with access to running wheels did not differ from young females. The number of viable conceptuses and fetal size were lower in both groups of aged females. Hundreds of genes were differentially expressed between young females and each of the aged groups, but only one gene was affected by access to running wheels. The placental transcriptomes of both aged groups were more similar to that of young mice at GD 10.5 than to young mice at GD 11.5, suggesting delayed placental development. Conclusions: Our model reproduced previously-reported effects of age on fetal development and placental transcriptomics, but these were not mitigated by increased voluntary locomotor activity, despite a reduction in adiposity. Remarkably, increased voluntary locomotor activity had almost no effects on placental gene expression in aged mice. To investigate whether increased locomotor activity could mitigate adverse pregnancy outcomes in a mouse model of advanced maternal age, we mated 3 groups of mice: Young (age range 12-20 weeks), Aged (age range 37-45 weeks), and Aged/Exercised (same as Aged, but provided running wheels 4 weeks prior to mating and throughout pregnancy). We collected placentas at GD 11.5 and also collected placentas from some Young mice at GD 10.5. We performed gene expression profiling analysis using data from RNA-seq.