The Moderately Aged Mouse: A Representative Model of Ageing in Pregnancy?

Abstract

A previous mouse model of advanced maternal age (AMA; 38-42 weeks) exhibits severe placental dysfunction, fetal growth restriction (FGR) and stillbirth rates, akin to women of AMA. Whilst useful for understanding the pathophysiology of placental disease, this model may not be optimal for testing new therapies due to the severe phenotype. Therefore, a moderately aged mouse (MAM; aged 28-32 weeks) model was developed, and the placental and maternal phenotypes, and fetal outcomes characterised; alongside a very advanced maternal age (VAMA) mouse, to provide a more continuous picture of advancing maternal age. It is hypothesised that MAM would exhibit an intermediate FGR phenotype, less severe than that of AMA mice, and that MAM would show elevated blood pressure (BP) and poorer glucose handling capacities than young control mice, but lower than those of AMA mice. Female C57BL/6J mice were mated at 8-16 weeks (young controls), 28-32 weeks (MAM), 38-42 weeks (AMA), or >42 weeks (VAMA), with 12–24-week-old male C57Bl/6J mice. BP was measured via tail cuff, glucose tolerance testing (GTT) was performed, mice were sacrificed, and tissues harvested. FGR was defined as fetal weight below the 5th percentile of young control weights. Placental tissue from the mouse models were immunohistochemically stained and quantified, alongside comparative human placental tissue from AMA and FGR groups, for a panel of cell cycle regulation, senescence and altered cell turnover markers. MAM saw 57% of pups

Date of Award	14 Feb 2023
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Mark Dilworth (Supervisor) & Alexander Heazell (Supervisor)