Altered smooth muscle development and innervation in the lower genitourinary and gastrointestinal tract of the male human fetus with myelomeningocele.

Abstract

We determine whether smooth and skeletal muscle or nerve density is altered in the lower genitourinary or gastrointestinal tract of male human fetuses with myelomeningocele at 20 weeks of gestation. We serially cross sectioned the lower genitourinary and gastrointestinal tracts in 7 male fetuses (mean age 20 weeks of gestation) with myelomeningocele and 4 age matched controls. Immunohistochemical staining was performed using Masson's trichrome stain and antibodies to smooth and skeletal muscle actin. S-100 protein staining for Schwann cell localization and neurofilament protein was also done. Fluorescein and rhodamine double immunolabeling was used to demonstrate the co-expression of smooth and skeletal muscle. Peripheral neural innervation of the bladder, prostate and rectum was markedly decreased in myelomeningocele. Masson's trichrome and smooth muscle actin staining also demonstrated that smooth muscle was less well differentiated in myelomeningocele specimens. Scant smooth muscle was present in the myelomeningocele bladder and bladder neck with an excess of collagen in an interfascicular and intrafascicular distribution. Double immunofluorescence staining revealed persistent co-expression of smooth and skeletal muscle actin by myocytes in the myelomeningocele detrusor, while in the control bladder there was only smooth muscle expression. The skeletal muscle component of structures in fetuses with myelomeningocele, including the external sphincter, was similar to that in controls. Prostatic size, ductal morphogenesis and smooth muscle were decreased compared to those in controls. A global defect exists in the development of smooth muscle in myelomeningocele in the lower genitourinary and gastrointestinal tracts by 20 weeks of gestation. Peripheral nerve density is decreased in smooth muscle in myelomeningocele, suggesting that an intact nervous system is important for the development of normal smooth muscle. Fetal surgery with coverage of the spinal cord in select cases may prevent progressive environmental injury to the somatic nervous system during the second half of gestation. However, achieving normal autonomic function is unlikely due to the extent of early global organ maldevelopment.