, Volume 15, Issue 2, pp 157-164

Effects of leptin, interleukin-1α, interleukin-6, and transforming growth factor-β on markers of trophoblast invasive phenotype

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Abstract

Phenotypic changes of integrin and metalloproteinase secretion of the invasive human cytotrophoblast are regulated by cytokines and growth factors, but how this occurs is not completely understood. We used 24h cytotrophoblast cultures from first trimester pregnancies to investigate the effects of leptin and cytokines on the expression of the α2, α5, and α6 integrin subunits and on the activity of metalloproteinase-2 (gelatinase A) and metalloproteinase-9 (gelatinase B). The α2 subunit was marginally upregulated by leptin and interleukin-1α (IL-1α). All compounds tested upregulated, in some degree, the α5 expression. The α6 integrin subunit was massively upregulated, by leptin, interleukins, and transforming growth factor-β. None of the factors tested affected metalloproteinase-2 activity, but the activity of metalloproteinase-9 was upregulated by leptin and IL-1α. In conclusion, leptin and IL-1α actively induce some of the changes that cytotrophoblasts undergo to achieve a more invasive phenotype. A novel role for leptin is proposed during early pregnancy: leptin might be an autocrine/paracrine regulator of cytotrophoblast invasiveness during implantation and placentation.