Ontology highlight
ABSTRACT: Placental dysplasia critically impairs fetal growth and development by disrupting nutrient supply. Thiamine, predominantly in its bioactive form thiamine pyrophosphate, serves as an essential coenzyme in mitochondrial energy metabolism, yet its regulatory role in placental development remains elusive. Objectives This study systematically unraveled the metabolic network disparities between sows with different reproductive potentials and elucidates the mechanisms by which characterized metabolites enhance placental angiogenesis and nutrient transport efficiency to promote fetal development. Methods We initially analyzed plasma and fecal metabolite composition and fecal microbial composition of sows with high and low reproductive potential by 16S rRNA sequencing and untargeted metabolomics. Subsequently, we evaluated the effects of thiamine, the identified characterized metabolite, on the angiogenesis and nutrient transport functions of placenta and the growth and development of offspring in a rat model, as well as verified the effects of thiamine on the cell migration of placental trophoblast cells by in vitro experiment. Results Sows with high reproductive potential exhibit a distinct metabolic profile with significantly elevated plasma arginine and fecal thiamine levels and the abundance of gut thiamine-synthesizing bacteria increases in parallel. Maternal thiamine supplementation effectively promotes offspring growth and enhances thiamine metabolism in the maternal-placental-fetal axis. Meanwhile, thiamine improves placental function by increasing thiamine-related metabolic enzymes and acetyl-CoA content in the placenta. Furthermore, thiamine facilitates placental angiogenesis via activation of the Notch signaling pathway and initiates the Notch-PI3K/AKT cascade reaction, which regulates placental nutrient metabolism efficiency and transporter expression. Conclusions Maternal supplementation with thiamine during gestation and lactation promotes placental development and enhances offspring growth through activation of the Notch signaling pathway.
INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase
PROVIDER: MTBLS12795 | MetaboLights | 2025-07-29
REPOSITORIES: MetaboLights