Upregulation of Interleukin-8 by Hypoxia in Human Ovaries


Address reprint requests to Yutaka Osuga, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
E-mail: yutakaos-tky@umin.ac.jp


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-1α/β, IL-8, and tumor necrosis factor (TNF)-α 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, IL-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.