Scanning electron microscopy of fetal murine myelomeningocele reveals growth and development of the spinal cord in early gestation and neural tissue destruction around birth

Abstract

Background: Previous studies demonstrated that the spinal cord within a fetal myelomeningocele (MMC) lesion suffers progressive destruction during gestation. This study aims at elucidating this pathophysiologic feature on a cellular and ultrastructural level in a model of genetically determined MMC.

Methods: Curly tail/loop tail mouse fetuses at various gestational stages and neonates were analyzed electron-microscopically to document time-point and nature of neural tissue development and pathologic alterations within the MMC.

Results: At embryonic day (E) 8.5 and E9.5, round cells displaying multiple microvilli covered the entire region of interest, and some specimens showed initial stages of neurulation. At E10.5, neurulation was terminated in normal animals, whereas the neural placode remained unfolded in MMC fetuses and became distinguishable from adjacent epidermal layers. At E15.5, an apparently normal differentiation was found. Until this time-point, there was no tissue damage or inflammation. Thereafter, increasingly severe tissue alterations were identified with ongoing gestation leading to almost complete loss of neural tissue at birth.

Conclusion: We show here in fetal mice with MMC that, apart from absent neurulation, growth and development of the otherwise perfectly intact exposed spinal cord appear normal in early gestation, whereas later, the unprotected neural tissue is progressively destroyed.