The Placental Stress Code: Lymphocyte Proliferation, Immune and Metabolic Enzyme Shifts Reveal Oxidative Stress in Preeclampsia and Preeclampsia with Gestational Diabetes Mellitus

Background: Preeclampsia (PE) and gestational diabetes mellitus (GDM) are complex pregnancy disorders characterized by hypertension, proteinuria, increased blood glucose levels, and metabolic dysfunction. Methods: We investigated lymphocyte proliferation, immune function, key antioxidants, and metabolic and mitochondrial enzyme activities in women with PE and PE with GDM compared to normotensive pregnant (NP) controls. Lymphocyte proliferation was assessed following phytohemagglutinin (PHA) stimulation at varying concentrations (0.5, 2.5, and 5 µg/mL). Activities of key antioxidant enzymes, metabolic enzymes, and mitochondrial enzymes were measured. Other stress markers, including nitric oxide (NO) production and lipid peroxidation (TBARS), along with acetylcholine esterase (AChE) activity, and proinflammatory cytokine assays (IL-6 and TNF-α) were also evaluated from the PHA-induced lymphocytes. Results: Lymphocyte proliferation in response to PHA was significantly increased in PE and PE with GDM groups compared to NP, although low-dose PHA (0.5 and 2.5 µg/mL) moderately enhanced proliferation in NP. IL-6 and TNF-α levels were notably elevated in both disease groups. Antioxidant activities of SOD, GST, GPx and AChE, Citrate synthase, Cytochrome c oxidase, and NO production were significantly reduced in PE and PE with GDM, while hexokinase activity involved in glycolysis was elevated in both groups. Further, TBARS levels were elevated in the disease groups, particularly in PE with GDM. Conclusions: The findings arise from a clinical cross-sectional study and highlight significant immune alterations, oxidative stress, and mitochondrial impairment in PE and PE with GDM. The observed elevation in proinflammatory cytokines further underscore the role of immune activation in the pathogenesis of these complications, emphasizing the integrated immunometabolic shifts identified in this study, as potential molecular indicators for early intervention.