The Amniotic Band Syndrome in the Rat Is Associated with the Activation of Transforming Growth Factor-β

Amniocentesis in rats is associated with different malformations, such as cleft palate and limb deformation, resembling the human congenital amniotic band syndrome (ABS). Despite many human cases reported in the literature, little is known about the mechanisms involved in ABS. This study addressed if the activation of the transforming growth factor-β1 (TGF-β1) pathway is, in part, associated with amniotic band formation and growth restriction induced in rats by amniocentesis, as by a previously published model. For this purpose, quantification of TGF-β1, α-smooth muscle actin, and collagen type I mRNA and protein levels were determined by quantitative PCR and Western blot analysis, respectively, in the fetus, its amniotic membrane, and the uterus of experimental and control rats. We found that TGF-β1 mRNA levels are increased in the fetus and the amniotic membrane at 6 hours, whereas α-smooth muscle actin, phosphorylated Smad3, and collagen type I increased at 48 hours, suggesting that a fibrotic response is induced after the amniotic sac puncture. Furthermore, fetuses had hemorrhages, syndactyly, and amputation of limbs, similar to human ABS.