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Tumor Necrosis Factor-Alpha Inhibits Ovulation and Steroidogenesis, but Not Prostaglandin Production in the Perfused Rat Ovary

Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah

C. Matthew Peterson

Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah

Murray D. Mitchell

Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah

Kirtly P. Jones

Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah

Harry H. Hatasaka

Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah

A. Marsh Poulson

Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah

OBJECTIVE: We tested the null hypothesis that tumor necrosis factor-alpha (TNF-alpha) does not decrease ovulation, estradiol and progesterone production, or prostaglandin (PG) E2,

PGF_2alpha, or 6 keto-PGF_1alpha production in the open bursa rat ovarian perfusion model.

METHODS: Experimental animals were controlled for age, weight, litter, and pregnant mare's serum gonadotropin (PMSG) aliquot. Female Sprague-Dawley rats, 26-27 days old, were injected with 25 IU PMSG. Forty-eight hours later, the right ovary was dissected, the bursa removed, and the specimen placed in the perfusion chamber with defined media. Luteinizing hormone and isobutylmethylxanthine were given as an ovulatory trigger. Test perfusions also received TNF-alpha in 0.8-nmol/L, -pmol/L, and -fmol/L doses. Samples were collected at 0, 1, 3, 5, 7, 10, and 20 hours. Ovulations were counted at 20 hours. Steroids and PGs were measured.

RESULTS: The addition of TNF-alpha to the rat ovarian perfusion model resulted in a dose- dependent decrease in ovulations (mean ± standard 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 inhibited estradiol (P < .005) and progesterone production (P < .05) throughout, but produced no significant changes in PG production.

CONCLUSION: Tumor necrosis factor-alpha inhibits ovulation in a dose-dependent fashion, and inhibits estradiol and progesterone production without altering PG production in the open bursa rat ovarian perfusion model. (J Soc Gynecol Invest 1994;1:59-64)

Key Words: Ovulation • TNF-alpha • cytokines.

Journal of the Society for Gynecologic Investigation, Vol. 1, No. 1, 59-64 (1994)
DOI: 10.1177/107155769400100112


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