Maternal vitamin A deficiency programs offspring visceral hypersensitivity through RARβ-COX-2/PGE2 signaling

Area of Science:

• Gastroenterology and Nutritional Science
• Developmental Biology
• Immunology

Background:

• Visceral hypersensitivity (VH) is a key factor in irritable bowel syndrome (IBS).
• Maternal vitamin A deficiency (VAD) is linked to offspring gastrointestinal issues, but its role in VH is unclear.
• Understanding the mechanisms behind VAD-induced VH is crucial for developing early interventions.

Purpose of the Study:

• To investigate the impact of maternal VAD on offspring VH development.
• To explore the underlying molecular mechanisms involving retinoic acid receptors and inflammatory pathways.
• To assess the therapeutic potential of postnatal vitamin A supplementation (VAS) and vitamin A (VA) intervention.

Main Methods:

• Utilized a maternal VAD rat model to study offspring VH.
• Analyzed intestinal retinoic acid receptor beta (RARβ), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) pathways in enteric glial cells (EGCs).
• Employed a sodium butyrate (NaB)-induced IBS model and in vitro EGC experiments to examine the effects of VA and retinoic acid (RA).

Main Results:

• Maternal VAD induced VH in offspring, characterized by downregulated RARβ and activated COX-2/PGE2/EP2 axis in EGCs.
• Postnatal VAS partially reversed these VH-associated changes.
• VA intervention in an IBS model alleviated VH and symptoms, potentially via suppression of the TLR4/MyD88/NF-κB pathway in EGCs.

Conclusions:

• Maternal VAD contributes to offspring VH through mechanisms involving RARβ and the COX-2/PGE2 pathway.
• Postnatal VAS and RA show therapeutic potential for VAD-induced VH and IBS-like symptoms.
• The RA-RARβ axis presents a potential target for early nutritional interventions in IBS.