MORPHOLOGICAL CLASSIFICATION OF NUCHAL SKIN IN HUMAN FETUSES WITH TRISOMY-21, TRISOMY-18, AND TRISOMY-13 AT 12-18 WEEKS AND IN A TRISOMY-16MOUSE

An increase in the nuchal translucency that can be detected at 10-14 w eeks of gestation by ultrasound forms the basis for a screening test f or chromosomal abnormality. Several mechanisms leading to this increas e in skin thickness have been proposed, including changes of the extra cellular matrix, cardiac defects and abnormalities of the large vessel s. This study examines the composition of the extracellular matrix of the skin in gestational age-matched fetuses with trisomy 21, 18 and 13 from 12-18 weeks. Immunohistochemistry was applied with monoclonal an d polyclonal antibodies against collagen type I, III, IV, V and VI and against laminin and fibronectin. Collagen type VI gene expression was further studied by in situ hybridization to detect differences in exp ression patterns of COL6A1, COL6A3 and COL1A1 between normal fetuses a nd those with trisomy 21. The ultrastructure of tissue samples was stu died by transmission electron microscopy (TEM) and additionally by imm unogold TEM. Further, we examined the morphology of the skin in an ani mal model for Down's syndrome, the murine trisomy 16, by light and TEM . The dermis of trisomy 21 fetuses was richer in collagen type VI than that of normal fetuses and other trisomies, and COL6A1, located on ch romosome 21, was expressed in a wider area than COL6A3, which is locat ed on chromosome 2. Collagen type I was less abundant in the skin of t risomy 18 fetuses, while the skin of all three trisomies contained a d ense network of collagen type III and V in comparison with normal fetu ses. Collagen type TV, of which two genes are located on chromosome 13 , was expressed in the basement membranes of the skin in all fetuses a nd additionally in the dermal fibroblasts only of trisomy 13 fetuses. Likewise, laminin was present in all basement membranes of normal and trisomic fetuses as well as in dermal fibroblasts of fetuses with tris omy Is. LAMA1 and LAMA3 genes are located on chromosome 18. Dermal cys ts were found in the skin of trisomy 18 and 13, but not in trisomy 21 and normal fetuses. Ultrastructural findings showed that an extracellu lar precipitate containing glycosaminoglycans was regularly present in the skin of trisomy 21 fetuses and murine trisomy 16 embryos. In conc lusion, this study suggests that the skin edema in fetal trisomies is characterized by specific alterations of the extracellular matrix that may be attributed to gene dosage effects as a result of a genetic imb alance due to the condition of fetal trisomy.