Maternal Immune Activation and Dietary Soy Isoflavone Supplementation Influence Pig Immune Function but not Muscle Fiber Formation

The goals of this study were to determine the impact of maternal PRRSV infection on offspring muscle and immune development and the potential of dietary soy isoflavones to mitigate those effects. Thirteen first-parity gilts ("gilts") were randomly allotted into one of three treatments: not infected and fed a diet devoid of isoflavones (CON), infected with porcine reproductive and respiratory syndrome virus (PRRSV) and fed the control diet (POS) or that supplemented with 1,500 mg/kg soy-derived isoflavones (ISF). Gilts were inoculated with PRRSV intranasally on gestational day (GD) 70. After farrowing (GD 114 ± 2), 1-2 offspring ("pigs") closest to the average litter weight were selected either at birth (3 ± 2 d of age) or weaning (21 ± 2 d of age) to determine body, muscle, and organ weights as well as muscle cell number and size. Four weaned pigs of average body weight within each litter were selected for postnatal immune challenge. At PND 52, pigs were injected with 5 µg/kg BW lipopolysaccharide (LPS) intraperitoneally. Serum was collected at 0, 4, and 8 h following LPS administration to analyze tumor necrosis factor alpha (TNF-α). At PND 59, pigs were administered a novel vaccine to elicit an adaptive immune response. At PND 59, 66, and 73, peripheral blood mononuclear cells were isolated and T-cell populations determined by flow cytometry. Both POS and ISF pigs exhibited persistent PRRSV infections throughout the study (PND 1-73). At PND 3, whole body, muscle, and organ weights were not different (P > 0.22) between groups, with the exception of relative liver weight, which was increased (P < 0.05) in POS compared with CON pigs. At PND 21, ISF pigs had reduced (P ≤ 0.05) whole body and muscle weights, but greater (P < 0.05) kidney weight compared with CON, and greater (P < 0.05) relative liver weight compared with CON and POS. Muscle fiber number and size were not different (P > 0.39) between groups at birth or weaning. After LPS administration, TNF-α was greatest in ISF pigs (P < 0.05) at both 0 and 8 h post-challenge. At the peak time-point of 4 h post-challenge, ISF pigs had the greatest concentration of TNF-α and CON pigs had the lowest, with POS pigs being intermediate (P = 0.01). After vaccination, ISF offspring had shifts in T-cell populations indicating an impaired immune response. These data indicate that maternal PRRSV infection may impact offspring organ growth and immune function, particularly when the dam is supplemented with isoflavones.Gestational health challenges may influence growth performance and immunity of offspring pigs during postnatal life. In particular, porcine reproductive and respiratory syndrome virus (PRRSV) is endemic in the U.S. herd, but its effects on surviving offspring pigs are largely unknown. Further, dietary supplementation with soy isoflavones lessened the severity of PRRSV infections in weaning and growing pigs. Therefore, the goals of this study were to determine the impact of maternal PRRSV infection on offspring muscle and immune development and the potential of isoflavones to mitigate those effects. Isoflavone supplementation reduced viral load in dams 21 d after infection, but did not alter clinical illness indicators. Pig mortality was increased by PRRSV infection in dams, and surviving pigs were infected with PRRSV throughout the study. Interestingly, muscle and organ weights were not different among treatments at birth, but infected litters were lighter at weaning, likely due to postnatal infection. Muscle fiber number and size did not differ between treatments. Pigs born to infected dams had slower responses during innate immune stimulation and then failed to mount a proper vaccine response during adaptive immune stimulation. Overall, maternal infection altered offspring immune responses but not muscle fiber development. Isoflavone supplementation did not mitigate these effects.