Longitudinal integrated evaluation of metabolic, inflammatory, biochemical, and hormonal biomarkers identifies haptoglobin as a key indicator of reproductive performance in Friesian-Holstein cows with endometritis under tropical Indonesian dairy conditionsia

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Background and Aim: Postpartum endometritis is a major cause of impaired fertility and economic loss in dairy production. Although metabolic, inflammatory, biochemical, and hormonal disturbances have individually been associated with uterine disease, comprehensive longitudinal evaluation of these physiological responses and their relationships with reproductive performance remains limited, particularly under tropical dairy production systems. This study aimed to longitudinally evaluate metabolic, inflammatory, biochemical, and hormonal biomarkers associated with uterine health and to determine their relationships with reproductive performance in Friesian-Holstein (FH) dairy cows with suspected and subclinical endometritis. Materials and Methods: Sixty multiparous FH dairy cows were classified by endometrial cytology into suspected endometritis (n = 30; polymorphonuclear neutrophils [PMN] 5%–<10%) and subclinical endometritis (n = 30; PMN ≥10%). Blood samples were collected on day 0 and day 30 to determine serum concentrations of non-esterified fatty acids (NEFAs), β-hydroxybutyrate (BHB), calcium (Ca), albumin, globulin, total protein (TP), haptoglobin (Hp), prostaglandin F₂α metabolite (PGFM), and cortisol. Uterine recovery was assessed by repeat cytology, while reproductive performance was evaluated using estrus intensity, service per conception (SC), and days open (DO). Statistical analyses included an independent-samples t-test, a paired-samples t-test, and a Pearson correlation analysis. Results: Cows with subclinical endometritis exhibited significantly greater uterine inflammation, higher PMN percentages, elevated NEFAs, BHB, Hp, PGFM, cortisol, globulin, and TP concentrations, and lower Ca and albumin concentrations than cows with suspected endometritis (p < 0.05). Recovery rates were lower in cows with subclinical endometritis (50.0%) than in those with suspected endometritis (83.3%). These cows also showed poorer reproductive performance, characterized by reduced estrus intensity, increased SC, and prolonged DO (p < 0.05). Among all evaluated biomarkers, Hp demonstrated the strongest associations with reproductive performance, showing a strong negative correlation with estrus intensity (r = −0.84) and strong positive correlations with SC (r = 0.84) and DO (r = 0.87) (p < 0.01). Longitudinal assessment further demonstrated partial physiological recovery between day 0 and day 30, although cows with subclinical endometritis consistently exhibited greater metabolic and inflammatory disturbances. Conclusion: Integrated longitudinal assessment demonstrated that systemic inflammation, metabolic imbalance, and endocrine alterations collectively influence uterine recovery and fertility in FH dairy cows. Hp emerged as the most informative biomarker, outperforming conventional metabolic indicators in its association with reproductive performance. These findings support incorporating Hp into biomarker-based reproductive monitoring strategies to identify cows at risk of poor fertility outcomes under tropical dairy production conditions. Keywords: Friesian-Holstein, haptoglobin biomarker, metabolic-inflammatory disturbances, postpartum endometritis, reproductive performance, tropical dairy cows.