Effects of maternal fructose, sucrose, and erythritol exposure on renal development and function in mouse offspring

Background Adverse maternal exposures during gestation and lactation may influence later renal health and susceptibility to chronic kidney disease (CKD). Whether maternal exposure to fructose, sucrose, and erythritol affects offspring renal development and function remains unclear. Methods Pregnant and lactating mice were administered fructose, sucrose or erythritol. Offspring renal development was assessed at 3 weeks via glomerular density and area. Renal structure, function, DNA damage, cell-cycle alterations, and molecular pathways were examined at 3 and 8 weeks. Transcriptomic, co-immunoprecipitation (Co-IP), immunofluorescence colocalization and in vitro assays were used to explore underlying mechanisms. Results Maternal exposure to fructose, sucrose, and erythritol was associated with reduced glomerular density in 3-week-old male offspring, with these alterations also observed at 8 weeks of age. At 8 weeks, male offspring exhibited decreased creatinine clearance, elevated kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in all sweetener-exposed groups, and increased urinary total protein in the erythritol group. Female offspring also showed alterations in glomerular area and histological features. Sweetener exposure was accompanied by increased DNA damage-related markers, PLK3 expression, and G2/M cell-cycle arrest in male offspring. PLK3 overexpression in vitro alters G2/M cell-cycle-related markers. Sucrose- and erythritol-exposed male offspring exhibited glucose intolerance and insulin resistance at 8 weeks. Conclusions Maternal exposure to fructose, sucrose, and erythritol during gestation and lactation was associated with renal developmental and functional alterations in male offspring, accompanied by PLK3 upregulation and G2/M cell-cycle-related alterations. In contrast, female offspring showed only mild histological changes.