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

Macarena Gonzalez , Eryk Andreas, Yasmyn Winstanley , Haley Connaughton, Karagh Loring, Cheryl Shoubridge , Rebecca Robker

Abstract

Context The age of childbearing has shifted in the last few decades, with more babies born to women over 30 years old. Increasing maternal age is associated with pregnancy and perinatal complications, such as reduced chance of conception, and higher risk of fetal death. 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). Mature female mice recapitulate many reproductive traits seen in older women, thus providing an ideal model for the study of maternal programming of offspring health. Aims In this study, we explored fecundity and offspring phenotype in female mice at the onset of reproductive aging. Methods First, we analyzed litter size and pup survival over time in breeder pairs. We then used female C57BL6/J mice at either 8 (young) or 40 (mature) weeks old to examine reproductive outcomes, and assessed their adult offspring growth, metabolic function, behaviour, and immune function. Key Results Female ageing reduced live birth rate, litter size and pup survival to weaning. Even though maternal ageing did not affect adult offspring immune function, their daughters were bigger, while their male littermates presented dysregulated glucose tolerance and higher hyperactivity levels. Conclusions These results indicate that maternal age reduces female fecundity and affects offspring adult health in a sex-specific manner. Implications Our study confirms the adverse effect of maternal age on adult offspring health, specially in male offspring, as this is relevant to human health.

RD24164  Accepted 15 February 2025

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