Effects of calcitriol upon TGF-βs and their receptors in trophoblast cells

Calcitriol levels increase during pregnancy, contributing to the hormonal and immunological balance, but its deficiency has been associated with problems during this period. Meanwhile, transforming growth factors-β (TGF-βs) play an important role in the maintenance of fetal-maternal immune tolerance; however, exacerbated concentrations of this growth factor are associated with complicated pregnancies. Therefore, we studied the effects of calcitriol on TGF-βs and their receptors in trophoblast cells. Term placentas from uncomplicated pregnancies after cesarean sections were used for cell cultures. Basal gene expression and the effect of calcitriol upon TGF-β1, TGF-β2, TGF-β3, and their receptors TGF-βR1 and TGF-βR2 were assessed using real-time PCR from trophoblast cells. The presence of TGF-β1, 2, 3, and TGF-βR1 were evaluated by immunofluorescence, and the protein abundance and secretion of TGF-β1 were assessed by Western blot and ELISA, respectively. Basal gene expression of TGF-β1 in trophoblast from term placentas was higher than TGF-β2 and TGF-β3, while TGF-βR2 was higher than TGF-βR1. The presence and cellular localization of TGF-β1, 2, 3, and TGF-βR1 were detected in the cytoplasm of syncytiotrophoblast, with TGF-β1 showing the highest intensity. Calcitriol significantly inhibited gene expression of TGF-β1, TGF-β2, and TGF-βR1. Likewise, calcitriol decreased the secretion and abundance of TGF-β1. In conclusion, results indicate that calcitriol is a regulator of TGF-βs in cultured trophoblast cells from term placentas and therefore may be an important player in the development of healthy pregnancies.