Female Reproductive Tract

Development and Use of an Ovarian Synchronization Model to Study the Effects of Endogenous Estrogen and Nitric Oxide on Uterine Blood Flow During Ovarian Cycles in Sheep

Abstract
The objective of the current study was to develop a ovine animal model for consistent study of uterine blood flow (UBF) changes during synchronized ovarian cycles regardless of season. Methods: Sheep were surgically bilaterally instrumented with uterine artery blood flow transducers, and 5-7 days later implanted with a vaginal progesterone (P4) controlled internal drug-releasing device (CIDR; 0.3g) for 7 days. On day 6 of P4 sheep were given two PGF₂ injections (7.5 mg I.M. 4 hours apart). At CIDR removal experimental Day 0, either 0 (n=9) 500 IU (n=8) or 1000 IU (n=7) of Pregnant Mare Serum Gonadotrophin (PMSG) was injected I.M.; UBF was monitored continuously for 55-75 hours. Jugular blood was sampled every 8 hours to evaluate levels of P4, Estradiol-17 (E₂) and Luteinizing Hormone (LH). The inhibitor of Nitric Oxide Synthase, L-Nitro-Arginine Methyl Ester (L-NAME) was infused in a step-wise fashion unilaterally into one uterine artery at 48-50 hours after 500 IU PMSG and the effects on UBF were examined (n=7). Results: The Zero PMSG group gradually increased UBF from a baseline of 17.4±3.9 to 80.5±1.1 ml/min. The 500 IU PMSG group increased UBF between 10-15 hours from a baseline of 11±3.3 to 83.3±1.0 ml/min whereas UBF for the 1000 IU group was higher (100.1±1.7 ml/min) than that seen in either of the other groups. Plasma P4 fell to baseline within 8 hrs of CIDR removal, while E₂ rose gradually in association with elevations in UBF. LH surges occurred between 32 and 56 hrs after CIDR removal and the LH surge occurred earlier in the 1000 IU PMSG group than the other two groups (P<0.01). L-NAME infusion dose dependently reduced maximum levels of UBF ipsilaterally by 54.6 ± 6.2%, but contralaterally only by 27.4 ± 8.5%. Conclusion: Regardless of season, either dose of PMSG will result in analogous UBF responses. During the follicular phase, elevations in UBF are in part locally controlled by the de novo production of Nitric Oxide.

Key words: Menstrual cycle • Nitric oxide • Seasonal reproduction • Steroid hormones • Uterus

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