Members of the
TGF-beta family have been shown to play an important role in numerous tissues during development. In the present study we have investigated the spatial and temporal expression of
TGF-beta 3, in human umbilical cord development. Total
TGF-beta 3 protein content, assessed by immunoblotting, increased with advancing gestation as did immunostaining and
mRNA in Wharton's jelly fibroblasts. Immunohistochemical analysis revealed that
TGF-beta 3 was present in all cell types. Temporal changes in
TGF-beta 3 expression were observed in the vascular smooth muscle cells, such that with advancing gestation
TGF-beta 3 protein expression and became mostly restricted to the extracellular compartment of the vascular media. This was associated with a decrease in
TGF-beta 3 mRNA expression in umbilical vascular smooth muscle cells. Of clinical significance, umbilical cords from pregnancies complicated by
pre-eclampsia, showed a significant reduction in total
TGF-beta 3 protein expression when compared to those of age-matched patients. Both
TGF-beta 3 mRNA and
protein expression were downregulated in the endothelium and smooth muscle layers of the umbilical arteries, as well as in the Wharton jelly fibroblasts. Our data demonstrate that during umbilical cord development
TGF-beta 3 expression is spatially and temporally regulated and that
TGF-beta 3 expression is altered in umbilical cords of pregnancies complicated by
pre-eclampsia. We speculate that the downregulation of
TGF-beta 3 expression found in pre-eclamptic umbilical cord may contribute to the abnormal structure and mechanical properties seen in these pathological umbilical cords.