EFFECTS OF MACROPHAGE-COLONY-STIMULATING FACTOR ON FOLLICULOGENESIS IN GONADOTROPIN-PRIMED IMMATURE RATS

The effect of macrophage colony-stimulating factor (M-CSF) on follicul ogenesis and ovulation was studied. Folliculogenesis and ovulation wer e induced in immature female rats with a s.c. injection of equine chor ionic gonadotrophin (eCG), followed 48 h later by human chorionic gona dotrophin (hCG). The ovulation rate was measured after the following t reatments. (I) Graded doses of human M-CSF (1-300 x 10(3) iu per rat) were administered i.p. daily for 3 consecutive days. (2) M-CSF (100 x 10(3) iu) was administered i.p. at designated times between 96 h befor e and 10 h after hCG injection. (3) Rabbit anti-human M-CSF polyclonal antibody (5 mu g) was administered into the left ovarian bursa at des ignated times between 49 h before and 10 h after hCG injection. In add ition, the effect of M-CSF on ovarian macrophages was investigated usi ng immunohistochemistry with mouse anti-rat macrophage monoclonal anti body, TRPM-3. The treatment with M-CSF (> 30 x 10(3) iu per rat) signi ficantly increased the ovulation compared with controls in a dose-depe ndent manner. This stimulatory effect of M-CSF was observed when it wa s administered between 96 h and 49 h before hCG injection. The ovarian intrabursal administration of anti-M-CSF antibody significantly inhib ited the number of ovulated ova from the treated ovaries compared with either those from control rats or from the contralateral untreated ov aries between 24 h before and 3 h after hCG injection. The immunohisto chemistry revealed that M-CSF increased the number of ovarian macropha ges in growing follicles. The results suggest that M-CSF is involved i n the process of folliculogenesis and that it promotes ovulation by in fluencing ovarian macrophages.