Effect of Timing of Dam Gestational Stress on Immune and Stress Responsiveness of the Progeny

Abstract Gestational stress may alter both the intrauterine environment and factors of passive immunity, which may affect the development of the immune system and the hypothalamic-pituitary-adrenal (HPA) axis of the progeny. Therefore, the objective was to determine if gestational stress and the stage of gestation at which stress occurred (mid vs. late) differentially affected the immune and stress variables of the offspring. First, parity gilts received either hydrocortisone acetate (HCA) or a placebo for 21 days at mid (d 51 to 72) or late (d 81 to 102) gestation to create a chronic psychological stress model. After farrowing, four piglets were tagged from each mid (M-HCA; n = 12), late (L-HCA; n = 12), and control (CON; n = 12) dam and followed through a 21-day lactation and 28-day nursery phase. Samples were obtained at birth, 7-, 14- and 21-days post birth (PB), and 24 hours, 7-, 14-, 21- and 28-days post-weaning (PW). A subset of piglets, balanced for dam treatment, body weight, and sex, were subjected to an ACTH challenge on day 21 PW consisting of an injection of ACTH (n = 12) or saline (n = 12). Data were analyzed utilizing the MIXED procedure of SAS with repeated measures. A treatment*day effect occurred for neutrophil (P < 0.0001) and lymphocyte (P < 0.0001) percentages and neutrophil-to-lymphocyte ratio (N:L; P < 0.0001). At birth, M-HCA piglets exhibited significantly less neutrophil and greater lymphocyte percentages than L-HCA or CON piglets. By day 14 PB, L-HCA piglets exhibited decreased neutrophil percentages. They tended to have greater lymphocyte percentages than M-HCA or CON piglets. On day 14PB, L-HCA piglets had the greatest N:L. Other immune measures like IgG and IgA plasma concentrations were also affected (P < 0.0001 for both; treatment*day); M-HCA piglets had less IgG on 7 PB than their counterparts and tended to have decreased IgA concentrations at birth and 21 PB in than CON piglets. Stress responsiveness of the progeny may have been affected by dam stress during gestation. For example, when challenged with ACTH, a significant treatment*injection*time effect was found (P = 0.0004). The ACTH-injected M-HCA piglets exhibited significantly greater plasma cortisol 1-h post-injection than ACTH-injected L-HCA or CON piglets and saline-injected M-HCA piglets. Notably, L-HCA was the only group not found to have a significant difference between ACTH and saline cortisol at 1 h. At 4-h post-injection, ACTH M-HCA piglets exhibited significantly less cortisol concentrations than their saline counterparts, while ACTH L-HCA piglets were still significantly greater at 24-h post-injection than their saline counterparts. Overall, these data suggest that stress during mid-gestation may have more of an effect on immune measures. In contrast, stress during late gestation may cause a diminished or delayed stress response in the progeny. Research is ongoing to characterize these immune and stress phenotypes further.