The Children's Center for Fetal Research, Children's Hospital of Philadelphia, The University of Pennsylvania School of Medicine, Abramson Research Center, Room 1116B, 3615 Civic Center Boulevard, Philadelphia, PA 19104-4318, USA.
To investigate whether myelomeningocele (MMC) is associated with a global neuromuscular maldevelopment of the lower gastrointestinal (GI) tract and anorectum, the distribution and staining intensity of non-neuronal (alpha-smooth-muscle-actin), neural crest cell (NCC, [Hoxb5]), and neuronal markers (PGP-9.5, synaptophysin, neurotubulin-beta-III) within the distal colon, rectum, and anal sphincters were analyzed by immunohistochemistry and Western blot in rat fetuses with retinoic acid (RA) induced MMC. At term (E22), no gross-morphological differences of the anorectal unit of OIL (n=21) MMC (n=31), and RA-exposed-non MMC (RA, n=19) fetuses were found. Smooth muscle cells were evenly distributed within the muscle layers of the rectum and the internal anal sphincter in OIL, MMC, and RA fetuses. Density and staining intensity of NCC and mature enteric neurons within the myenteric plexus of the distal colon and rectum and innervation pattern within anal sphincters in MMC fetuses were analogous to RA and OIL controls. Normal smooth muscle and myenteric plexus development of the rectum and normal innervation of the anal sphincters and pelvic floor suggests that MMC is not associated with a global neuromuscular maldevelopment of lower GI structures in this short-gestational model.
[Show abstract][Hide abstract] ABSTRACT: Nutritional deficiencies are preventable etiological and epigenetic factors causing congenital abnormalities, first cause of infant mortality. Folate deficiency has a well-established teratogenic effect, leading to an increasing risk of neural tube defects. This paper highlights the most recent medical literature about folate deficiency, be it maternal or paternal. It then focuses on associated deficiencies as nutritional deficiencies are multiple and interrelated. Observational and interventional studies have all been consistent with a 50-70% protective effect of adequate women consumption of folates on neural tube defects. Since strategies to modify women's dietary habits and vitamin use have achieved little progress, scientific as well as political effort is mandatory in order to implement global preventive public health strategies aimed at improving the alimentation of women in reproductive age, especially folic acid supplementation. Even with the recent breakthrough of fetal surgery for myelomeningocele, the emphasis should still be on prevention as the best practice rather than treatment of neural tube defects.
Journal of pregnancy 08/2012; 2012:295083. DOI:10.1155/2012/295083
[Show abstract][Hide abstract] ABSTRACT: Myelomeningocele (MMC) is a common and devastating malformation. Although fetal surgical closure may improve outcome, a less invasive approach that can be applied earlier in gestation is desirable. The objective of this study was to evaluate the therapeutic feasibility of a tissue engineering approach for prenatal coverage of MMC. A gelatin hydrogel composite combining a gelatin sheet and gelatin sponge was prepared with or without basic fibroblast growth factor incorporation, and applied prenatally to retinoic-acid-induced fetal MMC in the rat model. Most of the composites were adherent to the MMC within the amniotic fluid environment with the help of cyanoacrylate adhesive. Histological examination revealed cells layered over the composites with associated extracellular matrix as well as cellular ingrowth into the sponges. The layer over the composite was composed of mixed nonepithelial and epithelial cells with the extracellular matrix consisting of collagen type I and hyaluronic acid. The tissue inside the sponge consisted of nonepithelial cells and hyaluronic acid. Epidermal ingrowth underneath the sponges and neovascularization into the sponges occurred and were significantly increased by the incorporation of basic fibroblast growth factor. Although further development is needed, this study supports the therapeutic potential of a tissue engineering approach for prenatal coverage of MMC.
Tissue Engineering Part A 12/2009; 16(5):1645-55. DOI:10.1089/ten.TEA.2009.0532 · 4.64 Impact Factor
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