Embryonic factors mediate the maternal age-induced programming of offspring postnatal behavior in mice†

Embryos conceived by old females develop normally when surgically transferred to young recipients. Offspring conceived by old females display altered behaviors, even though they were prenatally and postnatally fostered by young females. Advanced maternal age is associated with adverse pregnancy and offspring outcomes, including neurodevelopmental disorders. While age-related oocyte and embryonic abnormalities may underlie this association, the aged maternal uterine environment also plays an important role in offspring development and survival. The aim of this study was to evaluate the contribution of maternal age-related embryonic and uterine factors on pregnancy and offspring behavior, by using a model of reciprocal embryo transfer between old and young female mice. Pregnancies were obtained by transferring embryos collected from either old (9-14 months) or young (3-4 months) C57BL/6J female mice to either young or old recipients. The results showed that embryos from old and young donors have comparable developmental potential when transferred to young recipients, whereas no pregnancies were obtained by transferring embryos of young females to old recipients. Moreover, the offspring conceived by aged females displayed altered ultrasonic vocalization and learning skills compared to the progeny of young females, even though they were both prenatally and postnatally fostered by young recipients. These results indicate that maternal factors mostly determine the occurrence of age-related pregnancy complications, whereas the long-term effects of maternal aging on the offspring's behavior could be already established at pre-implantation stages and depend on embryonic factors.