Effects of leptin, interleukin-1 alpha, interieukin-6, and transforming growth factor-beta on markers of trophoblast invasive phenotype

Phenotypic changes of integrin and metalloproteinase secretion of the invas ive human cytotrophoblast are regulated by cytokines and growth factors, bu t how this occurs is not completely understood. We used 24-h cytotrophoblas t cultures from first trimester pregnancies to investigate the effects of l eptin and cytokines on the expression of the alpha2, alpha5, and alpha6 int egrin subunits and on the activity of metalloproteinase-2 (gelatinase A) an d metal loproteinase-9 (gelatinase B). The alpha2 subunit was marginally up regulated by leptin and interleukin-1 alpha (IL-1 alpha). All compounds tes ted upregulated, in some degree, the alpha5 expression. The alpha6 integrin subunit was massively upregulated, by leptin, interleukins, and transformi ng growth factor-beta. None of the factors tested affected metalloproteinas e-2 activity, but the activity of metalloproteinase-9 was upregulated by le ptin and IL-1 alpha. In conclusion, leptin and IL-1 alpha actively induce s ome of the changes that cytotrophoblasts undergo to achieve a more invasive phenotype. A novel role for leptin is proposed during early pregnancy: lep tin might be an autocrine/paracrine regulator of cytotrophoblast invasivene ss during implantation and placentation.