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Published on: August 30, 2024
Pax3 mRNA is decreased in the hearts of rats with experimental diaphragmatic hernia
S Gonzalez-Reyes1, V Fernandez-Dumont, W Martinez-Calonge
1Departamento de Cirugia Pediatrica, Hospital Universitario "La Paz", P. de la Castellana 261, 28046 Madrid, Spain. jatovar.hulp@salud.madrid.org
Abstract:
Rats with nitrofen-induced congenital diaphragmatic hernia (CDH) have heart hypoplasia and cardiovascular malformations. The mechanism of action of nitrofen involves changes in neural crest signaling. Pax3 function is required for cardiac neural crest cells to complete their migration to the developing heart. The aim of this study was to examine whether Pa x 3 expression is changed at two gestational endpoints in rat embryos or fetuses exposed to nitrofen. On day E9.5 of gestation, pregnant rats received either 100 mg of nitrofen (n=10) or vehicle alone (control, n=10). The fetuses were recovered on E15 or E21. Their hearts were dissected out and weighed. Pax3 mRNA expression was determined by real-time polymerase chain reaction. We used two-tailed Student's t-tests to compare groups, with a threshold of significance of p<0.05. Compared with controls, nitrofen-exposed fetuses had heart hypoplasia in terms of heart/body weight ratio (0.62+/-0.10% vs. 0.77+/-0.17%, p<0.05). Pax3 mRNA expression in the heart was significantly decreased on E15 in nitrofen-treated embryos (32.94+/-17.11 U vs. 55.09+/-11.56 U, p<0.05), and it was still decreased, although not significantly, in the hearts of nitrofen-exposed fetuses recovered on E21 (15.67+/-5.56 U vs. 20.51+/-5.92 U, not significant). In conclusion, Pax3 is underexpressed in the hearts of nitrofen-exposed embryonal rats before the end of gestation. The mechanism of action of Pax3 should be further investigated because it could be one of the targets for future prenatal transplacental intervention.
Insights
Nitrofen exposure in rats causes congenital diaphragmatic hernia (CDH) with heart hypoplasia. This study found decreased Pax3 gene expression in affected embryonic rat hearts, suggesting a potential target for interventions.
Area of Science:
- Developmental Biology
- Genetics
- Toxicology
Background:
- Congenital diaphragmatic hernia (CDH) in rats induced by nitrofen is associated with heart hypoplasia and cardiovascular defects.
- Neural crest cell signaling is implicated in nitrofen's mechanism of action.
- Pax3 gene expression is crucial for cardiac neural crest cell migration to the developing heart.
Purpose of the Study:
- To investigate changes in Pax3 gene expression in rat embryos and fetuses exposed to nitrofen.
- To determine if Pax3 expression is altered at two specific gestational time points (E15 and E21) following nitrofen exposure.
Main Methods:
- Pregnant rats were administered nitrofen or vehicle on day E9.5 of gestation.
- Fetuses were collected on E15 and E21 for analysis.
- Heart-to-body weight ratio was measured to assess heart hypoplasia.
- Real-time polymerase chain reaction (PCR) was used to quantify Pax3 mRNA expression in heart tissues.
Main Results:
- Nitrofen-exposed fetuses exhibited significantly reduced heart-to-body weight ratios, indicating heart hypoplasia.
- Pax3 mRNA expression was significantly decreased in the hearts of nitrofen-exposed embryos on E15.
- While Pax3 expression remained lower in nitrofen-exposed fetuses on E21, the difference was not statistically significant.
Conclusions:
- Pax3 is underexpressed in the hearts of nitrofen-exposed rat embryos prior to term.
- The findings suggest that altered Pax3 expression is a consequence of nitrofen exposure during development.
- Pax3 may represent a therapeutic target for future prenatal interventions aimed at mitigating nitrofen-induced developmental defects.