Aim: 

In the human first-trimester placenta, extravillous trophoblast (EVT) cell proliferation, migration and invasiveness are modulated by several local factors, as well as by gap-junctional intercellular communications that, in turn, depend on connexin (Cx) expression. It has been shown that Cx40, Cx43 and Cx45 are expressed in EVT cells, where they are involved in the control of cell proliferation and differentiation. Cx expression is regulated by both growth factors and hormones like glucocorticoids. In the last years, ß-methasone administration in early gestation has been used to improve pregnancy outcome in women with idiopathic recurrent miscarriage. Indeed, this drug is able to reduce the uterine NK cell number, that is usually high in this pathologic condition. Aim of our study has been to verify whether ß-methasone could modulate Cx expression in HTR-8/SVneo cells, a well characterized model of human first-trimester EVT.

Methods and Results: 

Cx40 mRNA and protein are reduced by ß-methasone that, on the contrary, increases Cx43 and Cx45 mRNA and proteins. ß-methasone effects are not antagonized by RU-486, considered an anti-glicocorticoid, probably due to an interaction with different receptor isoforms (hGRa and hGCß). Immunofluorescence and ultrastructural studies support these results.

Conclusion: 

Since Cx are involved in the control of trophoblast functions, we hypothesize that ß-methasone exerts its protective action modulating these protein expression, besides reducing uterine NK cell number.