Leukemia Inhibitory Factor (LIF) and Vascular Endothelial Growth Factor (VEGF) diminish intensity of apoptosis in hypoxic human trophoblast: first- trimester versus term trophoblast cultures.

摘要

Leukemia Inhibitory Factor (LIF) and Vascular Endothelial Growth Factor (VEGF) influence trophoblast invasiveness and differentiation. Hypoxia disturbs these processes and induces apoptosis. Sensitivity of the human trophoblast to apoptotic stimuli is changing throughout pregnancy. We examined whether LIF- and/or VEGF-dependent changes in functional status of the cultured trophoblast cells influence apoptotic activity in hypoxic conditions. Placental samples were obtained after abortions in the first trimester (Group I) and after normal term pregnancies (Group II). The cytotrophoblast cells were isolated using trypsin-deoxyribonuclease digestion, followed by a Percoll gradient centrifugation. Established cultures within both groups were divided into 3 subgroups: LIF-(10ng/mL), VEGF- (100ng/mL) and LIF+VEGF-treated, cultured under hypoxia (2% O_2) for 48 hours. The cultures were terminated and quantitative determination of apoptosis was performed by ELISA, using cytokeratin-18 as an apoptosis marker. LIF, VEGF and LIF+VEGF produced decrease in intensity of hypoxia-related apoptosis. This anti-apoptotic influence was stronger in the first-trimester trophoblast. The differences in mean reduction of apoptosis intensity between Group I and II amounted to 76.09, 43.72 and 68.45 % (LIF-, VEGF- and LIF+VEGF-treated cultures, respectively; p<0.05). LIF- and VEGF-related effects on trophoblast cells may protect against hypoxia and consequently apoptosis, especially in the first-trimester of pregnancy.