Vitamin A supplementation during the suckling period attenuates the effects of a maternal Western diet on liver sexual maturity-related traits in a sex-dependent manner

Early-life overnutrition can alter puberty timing, in part through metabolic and hormonal signals produced or regulated by the liver. We investigated how a maternal Western Diet (WD) influences hepatic expression of puberty-related genes in mouse offspring, and whether early post-natal vitamin A (VA) supplementation —given as retinyl palmitate (RP) or β-carotene (BC)—can mitigate these effects. Dams were fed either a control diet or a WD throughout gestation and lactation, and offspring received a placebo, BC, or RP during suckling. Biometric parameters and the expression in the liver of puberty-related target genes and microRNAs at post-natal day 26 (PND-26) were assessed. Maternal WD increased body mass gain and fat accumulation in the offspring. Males showed a redistribution of fat toward visceral depots. Maternal WD upregulated the hepatic expression of Esr1 and adult liver sex-specific genes (Cyp2b9, Acot3, C6, and Gstp1). In males, it also upregulated sex hormone-dependent miR-125 family members and the puberty markers Igf1 and Kiss1. VA supplementation, particularly as RP, largely prevented the WD effects on liver gene expression in PND-26 male offspring without reducing WD-induced obesity. Effects in females were less consistent. In conclusion, developmental exposure to a WD promotes early pubertal traits in the offspring's liver, especially in males. Mild VA supplementation during suckling, particularly as RP, counteracts these molecular effects independently of obesity. The findings support the liver's emerging role in regulating puberty timing and the potential of early-life VA supplementation to prevent adverse effects of developmental overnutrition in offspring.