Immunometabolic-uterine-ovarian interactions and flushing therapy in dairy cows: a narrative review

Ovarian hypofunction is a major reproductive disorder in dairy cows and contributes substantially to reduced fertility, prolonged days open, and economic losses. Increasing evidence indicates that this condition is not solely an ovarian problem but part of a broader immunometabolic disturbance that also affects uterine health during the postpartum transition period. Negative energy balance after calving leads to elevated circulating metabolites such as non-esterified fatty acids and β-hydroxybutyrate, which trigger oxidative stress and inflammatory signaling. These changes impair hypothalamic-pituitary-ovarian activity, suppress steroidogenesis, and delay follicular development. At the same time, metabolic stress weakens uterine immune defense, slows uterine involution, and increases susceptibility to endometritis, creating a reciprocal cycle in which uterine inflammation further inhibits ovarian reactivation. This narrative review synthesizes current knowledge on the bidirectional interactions between ovarian function and uterine health from an immunometabolic perspective. A structured literature search of major scientific databases was conducted, focusing on peer-reviewed studies addressing postpartum metabolism, immune responses, reproductive physiology, and non-hormonal therapeutic approaches in dairy cows. The review integrates endocrine, metabolic, and inflammatory mechanisms into a unified framework explaining how immune-metabolic imbalance disrupts reproductive homeostasis. Within this framework, uterine flushing therapy is discussed as a practical non-hormonal intervention aimed at restoring uterine conditions rather than directly inducing ovulation. By removing inflammatory exudates, reducing endotoxin load, improving endometrial perfusion, and supporting immune resolution, flushing may indirectly promote normalization of hormonal signaling and ovarian activity. Field evidence suggests that, when combined with appropriate nutritional and herd management strategies, this approach can improve pregnancy outcomes and reduce reliance on repeated hormonal treatments. Overall, adopting an immunometabolic management strategy that integrates metabolic monitoring, uterine health assessment, and targeted supportive interventions offers a promising pathway to enhance reproductive efficiency and sustainability in modern dairy production systems. Further standardized field trials and biomarker-guided protocols are needed to validate these approaches and facilitate their wider on-farm implementation.