Maternal Exposure to Microplastics and High-Fructose Diet Induces Offspring Hypertension via Disruption of H₂S...

Maternal consumption of a high-fructose (HF) diet or exposure to microplastics (MPs) can each independently affect kidney development and increase the risk of hypertension in adult offspring, yet their combined impact remains poorly understood. Dysregulation of hydrogen sulfide (H₂S) signaling and alterations in gut microbiota are potential mediators of this programming. Pregnant rats received either standard chow or a 60% HF diet, with half of each group additionally exposed to sulfate-modified MPs (1 mg/L) with a 5 μm diameter throughout pregnancy and lactation. Male offspring were divided into four groups (n = 7-8 per group): control, HF, MP, and HF+MP. Maternal HF or MP exposure raised offspring blood pressure (BP), with additive effects when combined, and MP exposure caused renal injury. MP treatment also suppressed renal H₂S-generating enzymes and reduced H₂S production. Both HF and MP exposures altered gut microbial composition linked to BP regulation and induced metabolic changes in taurine/hypotaurine and sulfur pathways, suggesting impaired H₂S production. These results indicate that maternal HF and MP exposures interfere with H₂S signaling, gut microbiota, and metabolic programming, highlighting the H₂S signaling as a potential target to reduce long-term kidney and cardiometabolic risks.