Upregulation of interleukin-8 by hypoxia in human ovaries

PROBLEM: To evaluate the effect of hypoxia on interleukin (IL)-8 expression in human ovarian follicles. METHOD OF STUDY: Follicular fluid (FF) from each follicle was separately collected from women undergoing in vitro fertilization and embryo transfer. Concentrations of oxygen, progesterone, estradiol, IL-1alpha/beta, IL-8, and tumor necrosis factor (TNF)-alpha in FF were measured. Isolated granulosa-lutein cells (GLC) from obtained FF were cultured under normoxic or hypoxic conditions, and concentrations of IL-8 in culture media were measured. RESULTS: Simple regression analysis demonstrated a significant negative correlation between the concentrations of IL-8 and oxygen in FF (r = 0.50, P < 0.0001). However, none of the concentrations of progesterone, estradiol, 1IL-1β, and TNF-α in FF showed a significant correlation with IL-8 concentrations. Hypoxia stimulated the secretion of IL-8 by cultured GLC over twofolds compared with a normoxic control (P < 0.05). CONCLUSIONS: These findings suggest that IL-8, like other angiogenic factors, is upregulated under hypoxic condition, which argues that hypoxia in the ovarian follicles comes into play in ovarian functions by inducing a range of proangiogenic and chemoattractive substances.