Oxygen concentration modulates cellular senescence and autophagy in human trophoblast cells

Problem We investigated the effect of oxygen concentrations on cellular senescence and autophagy and examined the role of autophagy in human trophoblast cells. Method of study Human first‐trimester trophoblast cells (Sw.71) were incubated under 21%, 5%, or 1% O 2 concentrations for 24 hours. We examined the extent of senescence caused using senescence‐associated β‐galactosidase ( SA ‐β‐Gal) and senescence‐associated secretory phenotype ( SASP ) as markers. Moreover, we examined the role of autophagy in causing cellular senescence using an autophagy inhibitor (3‐methyladenine, 3 MA ). Results Physiological normoxia (5% O 2 ) decreased SA ‐β‐Gal‐positive cells and SASP including interleukin‐6 ( IL ‐6) and IL ‐8 compared with cultured cells in 21% O 2 . Pathophysiological hypoxia (1% O 2 ) caused cytotoxicity, including extracellular release of ATP and lactate dehydrogenase, and decreased senescence phenotypes. 3 MA ‐treated trophoblast cells significantly suppressed senescence markers ( SA ‐β‐Gal‐positive cells and SASP secretion) in O 2 ‐independent manner. Conclusion We conclude that O 2 concentration modulates cellular senescence phenotypes regulating autophagy in the human trophoblast cells. Moreover, inhibiting autophagy suppresses cellular senescence, suggesting that autophagy contributes to oxygen stress‐induced cellular senescence.