Abstract:
The precise regulation of extravillous trophoblast invasion of the uterine wall is a key process in successful pregnancies.
Kisspeptin (KP) has been shown to inhibit cancer cell metastasis and placental trophoblast cell migration. In this study
primary cultures of first trimester human trophoblast cells have been utilized in order to study the regulation of invasion
and angiogenesis-related genes by KP. Trophoblast cells were isolated from first trimester placenta and their identity was
confirmed by immunostaining for cytokeratin-7. Real-time quantitative RT-PCR demonstrated that primary trophoblast cells
express higher levels of GPR54 (KP receptor) and KP mRNA than the trophoblast cell line HTR8Svneo. Furthermore,
trophoblast cells also expressed higher GPR54 and KP protein levels. Treating primary trophoblast cells with KP induced
ERK1/2 phosphorylation, while co-treating the cells with a KP antagonist almost completely blocked the activation of ERK1/2
and demonstrated that KP through its cognate GPR54 receptor can activate ERK1/2 in trophoblast cells. KP reduced the
migratory capability of trophoblast cells in a scratch-migration assay. Real-time quantitative RT-PCR demonstrated that KP
treatment reduced the expression of matrix metalloproteinase 1, 2, 3, 7, 9, 10, 14 and VEGF-A, and increased the expression
of tissue inhibitors of metalloproteinases 1 and 3. These results suggest that KP can inhibit first trimester trophoblast cells
invasion via inhibition of cell migration and down regulation of the metalloproteinase system and VEGF-A.
