INTRODUCTION: The age at which women deliver their first child has increased steadily in recent years. Advanced maternal age (≥35 years) is associated with increased pregnancy complications (e.g., gestational diabetes mellitus and preeclampsia), in turn leading to maternal and perinatal morbidity and mortality. In a rat model of advanced maternal age, we have previously demonstrated maternal hypertension, fetal growth restriction and increased placental weight. We hypothesised that advanced maternal age affects placental function.
METHODS: Female Sprague Dawley rats aged 9-10 months (equivalent to a ~35 year old woman), and 4 months (young controls) were mated. On gestational day 20, fetal weights were recorded, and placentas were fixed for morphological assessment using stereology, or snap frozen for qPCR analysis of nutrient transporters and growth-regulatory genes.
RESULTS: Aged dams had a compromised capacity to carry viable pregnancies (young=90%, aged=50%), 40% smaller litters, and fetal weights were reduced by 10% compared to young dams. Preliminary data where fetal weight was assessed according to sex suggests that females from aged dams tended to be lighter. Placental weight was increased by 15% in aged dams, although calculated placental efficiency was reduced. There was no difference in the proportion of the placental zones, however the calculated volume of labyrinth and junctional zones were enlarged by 15% and 51%, respectively. Placentas from female fetuses from aged dams had increased expression of the glucose transport gene Slc2a3 (p<0.01) and amino acid transporter Slc38a4 (p=0.07). Nutrient transporter genes were unchanged in placentas from male fetuses from aged dams, but expression of angiogenic Vegf and the tumour suppressor p53, were reduced (p<0.05), compared to young dams.
CONCLUSION: Genes regulating placental nutrient transport, angiogenesis and apoptosis were altered in a sex-specific manner in aged dams. This provides insight into potential mechanisms responsible for poor pregnancy outcomes in advanced maternal age women.