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

Area of Science:

• Immunology
• Developmental Biology
• Molecular Biology

Background:

• Notch signaling is crucial for T cell development and immune function.
• Maternal exposure to staphylococcal enterotoxin B (SEB) during pregnancy affects offspring T cell populations.
• The impact of prenatal SEB exposure on the Notch pathway in T cell maturation is not fully understood.

Purpose of the Study:

• To investigate the effects of prenatal staphylococcal enterotoxin B (SEB) exposure on the Notch signaling pathway in developing thymocytes.
• To determine if prenatal SEB exposure alters the expression of Notch receptors, ligands, and downstream targets in the thymus.
• To examine the temporal dynamics of Notch signaling modulation by prenatal SEB exposure from neonates to adulthood.

Main Methods:

• Pregnant rats were exposed to staphylococcal enterotoxin B (SEB) or a control (PBS) on gestational day 16.
• Thymus tissues were collected from offspring at 14 days old (neonatal) and 3 months old (adult).
• Real-time PCR and western blot analyses were used to quantify the expression of Notch pathway components.

Main Results:

• Prenatal SEB exposure significantly downregulated Notch receptor and target gene expression in neonatal thymic T lymphocytes.
• Expression of Notch ligands in thymic stromal cells was also reduced in neonates exposed to SEB prenatally.
• In adult offspring, prenatal SEB exposure led to a significant upregulation of Notch receptors, ligands, and target genes compared to controls.

Conclusions:

• Prenatal SEB exposure induces a transient inhibition of thymic Notch signaling in early life.
• A compensatory upregulation of the Notch pathway occurs in adulthood, indicating dynamic reprogramming.
• These findings suggest that prenatal immune insults can have long-lasting, stage-specific effects on immune development via modulation of critical signaling pathways like Notch.