The Mechanism of Bladder Injury in Fetal Rats With Myelomeningocele.

Background: Bladder dysfunction has been implicated as a major cause of progressive renal failure in children with neurogenic bladder. However, its pathogenesis remains unclear. This study aimed to compare the expression of proliferation, apoptosis, and neuromuscular-related proteins during the development of the bladder in myelomeningocele fetal rats, and to explore the characteristics of its abnormal development. Methods: For the myelomeningocele group, Sprague Dawley pregnant rats were intragastrically injected with retinoic acid on the 10th day of gestation to induce myelomeningocele fetal rats. For the control group, the same amount of olive oil was injected to induce normal fetal rats. Bladders were harvested at embryonic days E16, E18, E20, and E22. Real-time quantitative polymerase chain reaction and western blotting were used to detect the protein levels of proliferating cell nuclear antigen (PCNA), cleaved caspase-3, neuron-specific nuclear-binding protein (NeuN), α-smooth muscle actin (α-SMA), and mRNA at E16-E22; immunohistochemistry was used to detect the expression of cleaved caspase-3 at E22. Results: The proliferation of bladder tissue cells was inhibited, with suppressed PCNA expression in myelomeningocele bladder tissue compared with that in control tissue at the early stage (E16). Myelomeningocele bladders showed increased tissue apoptosis in the late embryonic stage, with significantly higher cleaved caspase-3 protein expression than in the control bladders at E20 and E22. NeuN protein expression increased along with embryonic stage, although the expression at E20 and E22 was significantly lower in myelomeningocele bladders than in control bladders. α-SMA protein expression in myelomeningocele bladders increased gradually with the progression of pregnancy, although its expression was lower than that for control bladders at E22. Immunohistochemistry showed abundant positive staining for cleaved caspase-3 in the bladder mucosa and muscle layer of myelomeningocele bladders, and the expression of cleaved caspase-3 was significantly higher in myelomeningocele bladders than in control bladders. Conclusions: Bladder dysfunction in myelomeningocele fetal rats is related to the inhibition of proliferation, promotion of apoptosis, and reduction of bladder nerve and smooth muscle-related protein synthesis.