The potential role of aging on acute phase proteins and hypotalamus-pituitary-adrenal axis: a representative cohort study in pregnant mares

Pregnancy in mares triggers physiological adaptations involving changes in inflammatory biomarkers, particularly acute-phase proteins (APPs), and the activation of the hypothalamic–pituitary–adrenal (HPA) axis. However, the extent to which these responses are influenced by maternal age remains unclear. The hypothesis of this study was that both APP profile and HPA axis activity during gestation are modulated by the age of the mare. Accordingly, the objective was to evaluate these variables throughout pregnancy and assess the impact of age on their physiological regulation. A total of 41 Spanish Purebred mares were evaluated: n. 31 were pregnant (n. 15 of ≤10 years; n. 16 of >10 years old) and n. 10 were non-pregnant mares. Pregnant mares were monitored monthly throughout gestation, to assess temporal changes in APPs and HPA axis activity. Blood samples were collected to measure serum amyloid A (SAA), haptoglobin (Hp), C-reactive protein (CRP), adrenocorticotropic hormone (ACTH), and cortisol (CORT) concentrations. Statistical analysis included repeated measures ANOVA, and t -tests to assess biomarker differences by age and pregnancy status. Pregnant mares, particularly older individuals, showed elevated concentrations of inflammatory and endocrine markers compared to non-pregnant ones (p < 0.05). These findings demonstrate that pregnancy significantly alters inflammatory and endocrine biomarkers in mares; therefore, older pregnant individuals showed more pronounced and sustained increases compared to both younger pregnant and non-pregnant mares. This suggests that maternal age influences the physiological adaptation to pregnancy, particularly in the regulation of the HPA axis and acute-phase response.