TUMOR-NECROSIS-FACTOR-ALPHA INHIBITS OVULATION AND STEROIDOGENESIS, BUT NOT PROSTAGLANDIN PRODUCTION IN THE PERFUSED RAT OVARY

OBJECTIVE: We tested the null hypothesis that tumor necrosis factor-al pha (TNF-alpha) does not decrease ovulation, estradiol and progesteron e production, or prostaglandin (PG) E(2), PGF(2alpha), or 6 keto-PGF(1 alpha) production in the open bursa rat ovarian perfusion model. METHO DS: Experimental animals were controlled for age, weight, litter, and pregnant mare's serum gonadotropin (PMSG) aliquot. Female Sprague-Dawl ey rats, 26-27 days old, were injected with 25 IU PMSG. Forty-eight ho urs later, the right ovary was dissected, the bursa removed, and the s pecimen placed in the perfusion chamber with defined media. Luteinizin g hormone and isobutylmethylxanthine were given as an ovulatory trigge r. Test perfusions also received TNF-alpha in O.8-nmol/L, -pmol/L, and -fmol/L doses. Samples were collected at 0, 1, 3, 5, 7, 10, and 20 ho urs. Ovulations were counted at 20 hours. Steroids and PGs were measur ed. RESULTS: The addition of TNF-alpha to the vat ovarian perfusion mo del resulted in a dose-dependent decrease in ovulation (mean +/- stand ard deviation): 16.14 +/- 6.2 in controls (n = 7) versus 2.38 +/- 3.4 with TNF-alpha 0.8 nmol/L (n = 7), and 4.3 +/- 1.5 with TNF-alpha 0.8 pmol/L (n = 3), both P <.001. Tumor necrosis factor-alpha also inhibit ed estradiol (P <.005) and progesterone production (P <.05) throughout , but produced no sgnificant changes in PG production. CONCLUSION: Tum or necrosis factor-alpha inhibits ovulation in a dose-dependent fashio n, and inhibits estradiol and progesterone production without altering PC production in the open bursa rat ovarian perfusion model.