High fat, high carbohydrate (HFHC) diet-induced prediabetes as a risk factor for preeclampsia: assessing gender-specific infantile Sprague Dawley outcomes on selected markers of cardiovascular, haematological and cognitive function.

Abstract

Introduction. Pregestational prediabetes (PP), a precursor to type 2 diabetes and a risk factor for preeclampsia, profoundly affects the intrauterine environment, impairing cardiovascular, haematological, and cognitive development in offspring. This study investigates the impact of a high-fat, high-carbohydrate (HFHC) diet-induced prediabetic model on gender-specific infantile cardiovascular, haematological, and cognitive outcomes in Sprague-Dawley rat offspring. Methodology. Pups were born from dams with HFHC diet-induced prediabetes and L-NAME-induced preeclampsia (n=72) were divided into three groups: control (PCON), prediabetic (PPD), and preeclamptic (PPE). Offspring from each maternal group were divided into 2 subgroups. One subgroup was sacrificed at postnatal day 21 (n=36) for biomarker analysis which included BDNF and FGF2, while the second was retained until week 5 (n=36) for behavioural testing followed again by biomarker analysis specifically BDNF and FGF2. Cardiovascular parameters included mean arterial pressure (MAP), cardiac troponin I (cTnI), collagen I (COL I), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx). Cardiac tissue histology assessed cardiomyocyte size. Haematological evaluations included red blood cell markers [erythropoietin (EPO), red blood cell (RBC) count, haemoglobin (Hgb)], white blood cell markers [white blood cell count (WBC), granulocyte colony stimulating factor (G-CSF)], and platelet markers (platelet count) Neurodevelopmental assessments measured brain-derived neurotrophic factor (BDNF), fibroblast growth factor-2 (FGF2), and inflammatory cytokines (IL-6, IL-1β, TNF-α). Cognitive performance was evaluated using the Morris Water Maze (MWM) in the remaining pups (n=36) at five weeks Results. Cardiovascular biomarkers such as cTnI, COL I, and MAP were significantly elevated in PPD and PPE groups compared to PCON, with PPD showing the highest levels. Antioxidant enzymes (SOD, GPx) were significantly lower in PPD. Histological analysis revealed cardiomyocyte enlargement, particularly in PPD. In the haematological assessments, red blood cell indices were elevated in the PPD group, whereas haemoglobin concentration was reduced. White blood cell markers were higher in PPD, indicating inflammation. Platelet markers were altered in PPD, reflecting haemostatic disruption. Neurodevelopmental markers, including reduced BDNF and FGF2, were observed in PPD and PPE, alongside increased inflammatory cytokines. Male offspring showed more pronounced deficits than female offspring. Cognitive impairments assessed via MWM were more severe in PPD, correlating with altered hippocampal gene expression. Conclusion. In this study, the murine/rat model showed that PP exacerbates foetal dysfunction via intermediate hyperglycaemia, oxidative stress and inflammation highlighting the need for early, gender-specific interventions to mitigate long-term impacts in prediabetic pregnancies.