Abnormal development of the enteric nervous system in rat embryos and fetuses with congenital diaphragmatic hernia

Area of Science:

• Developmental biology
• Neuroscience
• Gastroenterology

Background:

• Congenital diaphragmatic hernia (CDH) survivors often experience esophageal and intestinal issues.
• Abnormal innervation of the esophagus and intestines has been observed in CDH patients and animal models.
• Previous studies indicated potential neural malformations in CDH.

Purpose of the Study:

• To investigate the effects of nitrofen exposure on the development of the enteric nervous system in rat embryos and fetuses.
• To characterize malformations in the esophagus and small bowel following prenatal nitrofen exposure.
• To correlate observed neural defects with potential causes of gastrointestinal morbidity in CDH survivors.

Main Methods:

• Pregnant rats were exposed to nitrofen or a vehicle control on embryonic day 9.5.
• Fetal tissues (esophagus, small bowel) were collected at embryonic days 15, 18, and 21.
• Histochemical staining for acetylcholinesterase (AChE) and immunohistochemistry for PGP9.5 were performed.
• Western blot (WB) and mRNA analysis of PGP9.5 were conducted.

Main Results:

• Deficient innervation was observed in the esophagus and small bowel of nitrofen-exposed fetuses at all studied time points.
• Western blot confirmed reduced PGP9.5 protein levels in E21 fetuses.
• PGP9.5 mRNA levels showed dynamic changes, decreasing at earlier time points and increasing later in specific tissues.

Conclusions:

• Prenatal exposure to nitrofen leads to deficient development of the enteric nervous system in the esophagus and small bowel.
• These neurodevelopmental anomalies are a potential contributing factor to the long-term gastrointestinal problems seen in CDH survivors.
• The study highlights the impact of specific teratogens on fetal gastrointestinal neurodevelopment.