Peritoneal macrophages modulate human granulosa-luteal cell progesterone production

Macrophages have been identified in the developing corpus luteum in several species, including man, and also constitute approximately 90% of cells in the peritoneal cavity. We studied the effect of peritoneal macrophages or blood monocytes on progesterone (P) synthesis by human granulosa cells from preovulatory follicles obtained at laparoscopy of 14 women undergoing in vitro fertilization. Pooled granulosa cells from follicles with mature ova were isolated by Ficoll-Hypaque gradient centrifugation. Washed granulosa cells (0.75 X 10(5)/ml) were incubated in Dulbecco's Minimum Essential Medium containing 20% calf serum with varying concentrations of pelvic macrophages (0.8-29 X 10(5)/ml) or fresh and mature blood monocytes (0.25-2.5 X 10(5)/ml). P production was determined by RIA of medium at 24-h intervals for 24-48 h. In situ concentrations of pelvic macrophages from 8 patients with tubal infertility increased cumulative P production to 140 +/- 17.8% (mean +/- SEM) of the control values. A similar increase (182 +/- 62.7%) was found with macrophages from 6 patients with endometriosis or unexplained infertility. Both fresh and mature monocytes stimulated P production to 225% and 261% of control values, respectively. Indomethacin (10(-4) M) or monoclonal antibody to somatomedin-C did not prevent stimulation of P production. These results suggest that peritoneal macrophages may exert luteotropic effects on cumulus cells while the ovulated oocyte resides in the tube, and incoming monocytes may be important in stimulating luteal cells in the developing corpus luteum.