62 Investigating maternal physiological responses to pregnancy in a guinea pig model of increased maternal stress

Abstract Abstract: Introduction Chronic maternal stress during pregnancy can have lasting impacts on both maternal health and fetal development, yet the underlying maternal physiological adaptations remain poorly understood. Objective Investigate increased chronic maternal stress, through food insecurity, on maternal physiological parameters at two gestational (GD) timepoints. Methods Female Hartley guinea pigs were fed either an ad libitum (Control) or a restricted diet (MNR) from 4 weeks prior to pregnancy until sacrifice. MNR dams were provided food at 1000h daily which was generally consumed within 4-6h leaving a period of ∼18-20h without food. Dams were euthanized at GD35-38 (mid-pregnancy: Control n = 7, MNR n = 6) or GD57-63 (near-term: Control n = 6, MNR n = 6) and weights recorded. Maternal plasma was analyzed for various metabolic markers. Statistical significance was determined using generalized linear modelling. Results While maternal weight (minus fetal and maternal-fetal interface weight) and maternal-fetal interface weight increased between timepoints (P < 0.001, both respectively), they remained similar between MNR and Control. MNR maintained litter size but had reduced fetal weight at both mid-pregnancy and near-term (13-19%; P = 0.014). Between mid-pregnancy and near-term, maternal cortisol (P = 0.041), glucose (P = 0.001), and calcium (P = 0.004) increased, while progesterone (P < 0.001), lactate (P < 0.001), and sodium (P = 0.021) decreased. MNR dams showed elevated cortisol (53-85%, P = 0.016), progesterone (13-35%, P = 0.036), and BUN (8-38%, P = 0.012) and reduced cholesterol (24-32%, P = 0.019) compared to Controls at both gestational timepoints. Conclusion Chronic maternal stress from before pregnancy leads to a metabolic state characterized by elevated cortisol and altered energy utilization (increased BUN, decreased cholesterol), suggesting metabolic adaptations to prioritize maternal survival but with compromised fetal growth. (Supported by NIH K99HD109458 & R01HD090657)