(P27-015-23) Ischemic Outcome in Young and Adult Male and Female Offspring After Maternal Deficiencies in One-Carbon Metabolites During Pregnancy and Lactation

Objectives: Maternal one-carbon metabolism, including dietary levels of folic acid and choline, play an important role in early life programming. There is a well-established connection between the fetal environment and the health status of offspring. However, there is a gap in knowledge on how maternal nutrition will affect the health status of the offspring after a cardiovascular event like ischemic stroke. The aim of our study was to investigate the role of maternal dietary deficiencies in folic acid or choline on stroke outcome in 3- and 11-month-old male and female offspring.

Methods: Adult female mice were fed a folic acid deficient diet (FADD), a choline deficient diet (ChDD), or a control diet (CD) four weeks prior to pregnancy to deplete stores, they were continued on diets during pregnancy and lactation. Male and female offspring were weaned onto a control diet and at 2 or 10 months of age were subject to ischemic stroke within the sensorimotor cortex via the photothrombosis ischemic damage model. At 3 or 11 months of age, motor function was measured in offspring and tissue was collected for analysis.

Results: Mothers maintained on either a FADD or ChDD had reduced levels of S-adenosylmethionine in liver tissue compared to controls. In offspring after ischemic stroke, motor function was impaired in 3-month-old male and female offspring from deficient mothers compared to control diet offspring. In 11-month-old mice there was no impact of maternal diet on motor function, but we observed sex differences. Male middle-aged adult mice had worse motor function compared to female offspring. In brain tissue, there was no impact of maternal diet on ischemic damage volume in 3-month-old animals. Interestingly, maternal diet impacted 10-month-old male and female offspring. Neurodegeneration and choline metabolism in ischemic brain tissue was impacted in both 3 and 11-month-old offspring.

Conclusions: The findings of our study suggest that a maternal diet deficient in either choline or folic acid impacts stroke outcome in young animals compared to middle-aged animals. This result points to the important role of the maternal diet in early life programming, while emphasizing its effects on both fetal development and long-term cerebrovascular health.

Funding Sources: American Heart Association (Nafisa M. Jadavji; 20AIREA35050015)