Angiotensin II induces apoptosis in human mural granulosa-lutein cells, but not in cumulus cells

Objective: To test whether angiotensin II (AngII) could modulate apoptosis of human granulosa-lutein (GL) cells from gonadotropin-stimulated follicles. Design: In vitro assays on mural and cumulus granulosa cells. Setting: University laboratory and private IVF practice. Patient(s): One hundred six consecutive women undergoing 113 IVF cycles. Intervention(s): Purified human GL mural or cumulus cells were cultured in serum-free media in the presence or absence of AngII with or without the AngII receptor blockers saralasin and CGP42112A. Main Outcome Measure(s): Detection of apoptosis using a fluorescent in situ marker for activated caspases. Result(s): Mural cells had approximately eightfold the amount of apoptosis compared with cumulus cells (average 0.23 vs. <0.03, respectively). With mural cells, AngII increased GL cell apoptosis versus untreated control samples (AngII 10-11 mol/L +6.5%; AngII 10―9 mol/L +13.3%, and AngII 10―7 mol/L +11.3%), an effect which was blocked by concurrent incubation with AngII receptor blockers. The AngII receptor blockers produced a significant decrease of apoptosis compared with control cultures (saralasin: 19.4%; CGP42112A: 28.9%). Neither AngII nor blockers had effect on cumulus cells. Conclusion(s): Preovulatory concentrations of AngII, most likely via AT2 receptors, increase apoptosis of cul- tured mural GL cells but have no effect on cumulus cells. Granulosa cells appear to be differentially regulated by AngII.