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

## TL;DR

This study finds that early-onset negative energy balance in dairy cows increases the risk of retained fetal membranes, affecting their health and productivity.

## Contribution

The study identifies early metabolic dysregulation as a novel predictor of retained fetal membranes in dairy cows.

## Key findings

- RFM cows showed significant negative energy balance 21 days before calving, marked by elevated fatty acids and reduced antioxidant activity.
- Metabolomic analysis revealed lipid and amino acid imbalances in RFM cows from 21 days prepartum to 4 hours postpartum.
- Metabolic dysfunction in placenta and fetal membranes impairs energy supply and immune homeostasis, delaying membrane expulsion.

## Abstract

Retained fetal membrane (RFM), a significant reproductive disorder in dairy cattle, adversely affects both animal health and production efficiency. It is concerning that the underlying pathogenesis of RFM remains incompletely elucidated. In this trial, a longitudinal approach was employed to investigate the metabolic dysregulation associated with RFM by analyzing temporal changes in plasmic biochemical parameters and metabolomic profiles at key periparturient time points (21 and 7 d prepartum and 4 h postpartum) in primiparous RFM dairy cows. By integrating these findings with metabolomic data from placental tissues and the fetal membranes themselves, we seek to interpret the physiological functional alterations occurring in the prepartum period of RFM cows from a metabolic perspective. The ultimate goals are to establish high-specificity predictive biomarkers for RFM and to advance mechanistic understanding of RFM pathogenesis through metabolic pathway analysis.

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) (p ≤ 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.