Caught in the metabolic NET: Neutrophil dysfunction and endometrial health in transition dairy cows

Korte beschrijving

The transition period is among the most physiologically demanding stages of the dairy cow's productive life. The onset of lactation sharply increases energy and nutrient demands that voluntary feed intake cannot yet meet, resulting in negative energy balance (NEB), adipose tissue mobilization, elevated non-esterified fatty acids (NEFA), disrupted glucose homeostasis, and altered inflammatory regulation. These systemic changes coincide with a critical local challenge: the postpartum uterus must undergo involution and mount an effective immune response against bacterial contamination. Yet bacterial exposure alone cannot account for the wide variation in disease outcome among cows under similar conditions, pointing to host-related factors—particularly the systemic metabolic and immune adaptations of the transition period—as key determinants of uterine disease susceptibility and severity. Building on this rationale, the present thesis was designed to test the central hypothesis that postpartum uterine disease in dairy cows is not solely a consequence of microbial infection but rather emerges from a broader immune-metabolic framework in which systemic metabolic stress, polymorphonuclear leukocytes (neutrophil; PMN) functional reprogramming, and endometrial immune responses converge to shape uterine health and disease outcomes. To address this hypothesis, the thesis integrated methodological optimization, functional PMN assays, transcriptomic analyses, and both in vitro and ex vivo experimental models, complemented by endometrial profiling of cows diagnosed with clinical endometritis (CE) or subclinical endometritis (SCE).