Visfatin exerts an anti-proliferative and pro-apoptotic effect in the human placenta cells†

Visfatin regulates energy homeostasis, metabolism, inflammation, and reproduction via the hypothalamus-pituitary-ovary axis. Our previous study showed the visfatin gene and protein expression in the human placenta. This study aimed to investigate the in vitro effect of visfatin on the proliferation and apoptosis of placental JEG-3 and BeWo cells but also in villous explants collected from normal pregnancies and complicated by intrauterine growth restriction (IUGR), preeclampsia (PE), and gestational diabetes mellitus (GDM). We studied placenta cells viability, proliferation, cell cycle, proliferation/apoptotic factors and insulin receptor (INSR) expression, DNA fragmentation, CASP3/7 activity, and phosphorylation of ERK1/2, AKT, AMPK alpha, STAT3 with their involvement after pharmacological inhibition in visfatin action on proliferation and apoptosis. Visfatin (1, 10, 100 ng/mL) decreased the viability and proliferation of JEG-3 after 48 h, and a similar effect was observed via co-administration of visfatin (10 ng/mL) and insulin (10 ng/mL) in JEG-3 and BeWo after 48 h and 72 h, respectively. Visfatin reduced the transition from the G2/M phase, and expression of PCNA or cyclins D, E, A, and B in JEG-3 and PCNA in normal, IUGR, PE, and GDM placentas. It increased DNA fragmentation, CASP3/7 activity, P53, BAX/BCL2, CASP9, CASP 8, CASP3 levels in BeWo, and CASP3 expression in tested placentas. Furthermore, visfatin modulated INSR, ERK1/2, AKT, AMPK alpha, and STAT3 expression in JEG-3 and BeWo, and its anti-proliferative and pro-apoptotic effects occurred via mentioned factors. In conclusion, visfatin, by affecting the proliferation and apoptosis of human placenta cells, may be an important factor in the development and function of the organ. Sentence Visfatin exerts an anti-proliferative and pro-apoptotic effect in the human placenta via insulin receptor, ERK1/2, AKT, AMPK alpha, and STAT3 signaling pathways.