Related Experiment Video
Updated: Jun 12, 2026
Generating a Reproducible Model of Mid-Gestational Maternal Immune Activation using Poly(I:C) to Study Susceptibility and Resilience in Offspring
Published on: August 17, 2022
Maternal vitamin A deficiency programs offspring visceral hypersensitivity through RARβ-COX-2/PGE2 signaling
Mengxia Tang1, Lue Gou1, Wenzhi Bao1
1Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, China; Guizhou Children's Hospital, China; Guizhou Biomanufacturing Laboratory, Affiliated Hospital of Zunyi Medical University, China.
Insights
Maternal vitamin A deficiency (VAD) in rats caused visceral hypersensitivity (VH) in offspring. Postnatal vitamin A supplementation (VAS) partially reversed these effects, suggesting a nutritional link to IBS development.
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.
Abstract:
Visceral hypersensitivity (VH) is regarded as a core pathophysiological mechanism in irritable bowel syndrome (IBS). Although maternal vitamin A deficiency (VAD) during pregnancy has been linked to gastrointestinal dysfunction in offspring, its specific role in VH and the underlying mechanisms are not yet fully understood. This study aimed to explore the effects of maternal VAD on the development of VH in offspring and to assess the potential therapeutic role of postnatal vitamin A supplementation (VAS). Using a maternal VAD rat model, we observed that maternal VAD was associated with the development of VH in offspring, along with downregulated intestinal retinoic acid receptor β (RARβ) and activation of the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2)/prostaglandin E2 receptor EP2 (EP2) axis in enteric glial cells (EGCs). These changes could be partially reversed by postnatal VAS. In a NaB-induced IBS model, VA intervention appeared to alleviate VH, gastrointestinal dysmotility, and diarrhea-like symptoms, possibly through suppression of the TLR4/MyD88/NF-κB pathway. In vitro experiments indicated that retinoic acid (RA), the active metabolite of VA, may inhibit TLR4/MyD88/NF-κB activation in EGCs, leading to reduced COX-2 expression and PGE2 synthesis. These findings suggest a nutritionally regulated mechanism linking maternal VA status to offspring VH and raise the possibility that the RA-RARβ axis may serve as a potential target for early nutritional interventions in IBS.
