Prenatal SEB Exposure Triggers Biphasic Notch Signaling Modulation in Offspring Thymus From Neonatal Suppression to Adult Activation

Notch signaling pathway modulates immune function by regulating T cell development, differentiation, and function. Previous studies from our group have demonstrated that maternal exposure to staphylococcal enterotoxin B (SEB) during pregnancy alters T cell frequencies in offspring. To further investigate the underlying mechanisms, we examined the impact of prenatal SEB exposure on the Notch signaling pathway, a critical regulator of thymic T cell maturation. In this study, pregnant rats were injected with 15 μg SEB on gestational day 16. Thymus tissues were aseptically collected from 14-day-old and 3-month-old offspring in both the PBS and SEB-exposed groups. The expression of Notch pathway components-including receptors, ligands, and downstream target genes-was assessed using real-time PCR and western blot. It was found that prenatal SEB exposure significantly downregulated mRNA and protein levels of Notch receptors and target genes in thymic T lymphocytes in neonatal offspring. Additionally, ligand expression was reduced in thymic stromal cells. Strikingly, this suppression was reversed in adulthood, with SEB-exposed offspring exhibiting elevated expression of Notch receptors, ligands, and target genes. These results indicate that prenatal SEB exposure transiently inhibits Notch signaling in neonatal thymocytes but leads to a compensatory upregulation in adulthood. This biphasic modulation suggests that prenatal SEB exposure can induce long-term, dynamic reprogramming of thymic Notch signaling, with potential implications for T cell-mediated immunity across developmental stages.