Trophoblast cell invasion is tightly controlled during pregnancy, but aberrant invasion is associated with placental diseases such as preeclampsia. The protein EGF is known to exert a proinvasive effect on trophoblast cells through its receptor, EGFR, but the mechanism remains unclear. To learn more, researchers recently conducted in vitro studies on a human trophoblast cell line treated with EGF. They found that EGF reduced the expression and secretion of KISS1, a gene encoding the tumor metastasis-suppressing protein kisspeptin by activating the EGFR-mediated PI3K/AKT signaling pathway. EGF also downregulated ID3 expression, an effect that was required for EGF-mediated KISS1 suppression. Functional assays confirmed that EGF-induced KISS1 downregulation stimulated human trophoblast cell invasion and analyses of clinical samples revealed that patients with preeclampsia (PE) had reduced serum EGF levels and increased serum and placental KISS1 levels. Although further research on primary cells is needed, the results reveal a mechanism of preeclampsia pathogenesis and enhance understanding of KISS1 regulation and the roles of EGF/EGFR in the human placenta.