Cytokine Expression and Haptoglobin Levels in Bovine Fetuses Spontaneously Aborted by Intracellular Infectious Agents and by Probable Infectious Etiology

Abstract

Cattle abortions pose a serious challenge to livestock health and farm income, yet many cases lack a clear cause even when signs of infection are present. We examined immune activity in aborted bovine fetuses at mid and late gestation caused by three common agents that invade cells, comparing them with fetuses showing infection-like lesions without a known cause and with healthy controls. In mid-gestation losses by intracellular agents, we found a surge in proteins that drive inflammation, indicating a strong early defensive reaction. In contrast, late-pregnancy losses showed a drop in those inflammatory signals, suggesting a shift toward a more subdued immune state. Fetuses with unknown infections also showed distinct patterns. Although differences in haptoglobin levels were observed in mid-gestation fetuses aborted due to intracellular agents compared to controls, the overall concentration remained low and may be of limited biological relevance. Variations in the fetal immune response according to pathogen type and gestational stage provide novel insights into the pathogenesis of key intracellular agents, thereby strengthening diagnostic approaches and contributing to improved herd health and agricultural sustainability. Intracellular pathogens such as Neospora caninum, Brucella abortus, and Bovine Viral Diarrhea Virus (BVDV) are major contributors to bovine abortions, yet many cases remain without a definitive etiological diagnosis despite inflammatory evidence. This study aimed to characterize the immune response in bovine fetuses aborted due to these intracellular agents, comparing them with fetuses showing inflammatory lesions of probable infectious origin and with negative controls. We analyzed cytokine expression (IFN-γ, TNFα, IL- 4, IL-8, IL-12) and haptoglobin levels in mid- and late-gestation fetuses. Mid-gestation fetuses infected with intracellular agents exhibited elevated IFN-γ and IL-8 expressions,suggesting a Th1-type immune response, while late-gestation fetuses showed decreased of these cytokines, indicating a shift toward a Th2-type response. Probable infectious abortions at late gestation also showed downregulation of IFN-γ. No significant differences were observed in TNF-α and IL-12 expressions. Additionally, haptoglobin levels were lower in mid-gestation infected fetuses compared to controls. These findings highlight gestational age-dependent immune modulation in response to intracellular infections and suggest that other unidentified pathogens may contribute to abortions with inflammatory lesions but no confirmed etiology. This study enhances our understanding of fetal immune responses in bovine abortions and may support improved diagnostic approaches for reproductive losses in cattle.