Early-Onset Negative Energy Balance in Transition Dairy Cows Increases the Incidence of Retained Fetal Membranes

This study investigated the metabolic mechanisms driving physiological functional remodeling in RFM by analyzing plasma biochemical parameters and metabolomic profiles at key peripartum timepoints (21 and 7 d prepartum and 4 h postpartum), integrated with placental and fetal membrane metabolic characteristics. The results revealed that RFM cows exhibited significant negative energy balance (NEB) as early as 21 days before parturition, characterized by elevated plasma levels of non-esterified fatty acids, β-hydroxybutyrate, and malondialdehyde, alongside reduced activity of antioxidant enzymes (GSH-Px, CAT) (<i>p</i> ≤ 0.05). Metabolomic analysis demonstrated persistent lipid metabolism dysregulation, amino acid imbalance, and nucleotide metabolism disturbances in RFM cows from 21 days prepartum to 4 h postpartum, indicating premature mobilization of adipose and muscle tissues. Further metabolomic analyses of the placenta and fetal membranes confirmed that metabolic dysfunction compromises energy supply during parturition, adversely affecting immune homeostasis and extracellular matrix degradation in the placenta and fetal membranes of RFM dairy cows. These physiological dysfunctions have the potential to impede the timely expulsion of fetal membranes after calving. In conclusion, RFM is closely associated with early-onset metabolic dysfunction during the periparturient period, where insufficient energy supply due to NEB, oxidative stress, and immune-endocrine disruptions collectively impair normal fetal membrane detachment.