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BOR - Papers in Press, published online ahead of print February 25, 2004.
Biol Reprod 2004, 10.1095/biolreprod.103.019901
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BIOLOGY OF REPRODUCTION 70, 1886–1894 (2004)
DOI: 10.1095/biolreprod.103.019901
© 2004 by the Society for the Study of Reproduction, Inc.


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 Sheep1

Tiffini C. Gibson3,5, Terrance M. Phernetton3, Milo C. Wiltbank4, and Ronald R. Magness2,3,5,6

Departments of Obstetrics and Gynecology,3 Dairy Science,4 Animal Sciences,5 Pediatrics,6 University of Wisconsin-Madison, Madison, Wisconsin 53706

The objective of the current study was to develop an ovine animal model for consistent study of uterine blood flow (UBF) changes during synchronized ovarian cycles regardless of season. 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; 0.3 g) for 7 days. On Day 6 of P4, sheep were given two prostaglandin F2{alpha} injections (7.5 mg i.m. 4 h apart). At CIDR removal, Experimental Day 0, zero (n = 9), 500 IU (n = 8), or 1000 IU (n = 7) eCG was injected i.m.; UBF was monitored continuously for 55–75 h. Jugular blood was sampled every 8 h to evaluate levels of P4, estradiol-17ß (E2ß) and luteinizing hormone (LH). The inhibitor of nitric oxide synthase, L- nitro-arginine methyl ester (L-NAME) was infused in a stepwise fashion unilaterally into one uterine artery at 48–50 h after 500 IU eCG and the effects on UBF were examined (n = 7). The zero-eCG group gradually increased UBF from a baseline of 17.4 ± 3.9 to 80.5 ± 1.1 ml/min. The 500-IU-eCG group increased UBF between 10 and 15 h from a baseline of 11 ± 3.3 to 83.3 ± 1.0 ml/min, whereas UBF for the 1000-IU-eCG 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 h of CIDR removal, while E2ß rose gradually in association with elevations in UBF. LH surges occurred between 32 and 56 h after CIDR removal and the LH surge occurred earlier in the 1000-IU-eCG 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%. Regardless of season, either dose of eCG 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.

1 Supported in part by National Institutes of Health grants HL49210, HL57653, HD33255, and HD38843. This study is in partial fulfillment of the M.S. degree for T.C.G.

2 Correspondence: Ronald R. Magness, Department of Obstetrics and Gynecology, University of Wisconsin, Perinatal Research Laboratories, 7E Meriter Hospital, 202 South Park Street, Madison, WI 53715. FAX: 608 257 1304; rmagness{at}wisc.edu




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