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BOR - Papers in Press, published online ahead of print August 6, 2003.
Biol Reprod 2003, 10.1095/biolreprod.103.016212
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BIOLOGY OF REPRODUCTION 69, 1907–1913 (2003)
DOI: 10.1095/biolreprod.103.016212
© 2003 by the Society for the Study of Reproduction, Inc.

Female Reproductive Tract

Roles of Tumor Necrosis Factor-{alpha} of the Estrous Cycle in Cattle: An In Vivo Study1

Dariusz J. Skarzynski2,3, Mamadou M. Bah3, Katarzyna M. Deptula3, Izabela Woclawek-Potocka3, Anna Korzekwa3, Masami Shibaya4, Wojciech Pilawski3,5, and Kiyoshi Okuda4

Division of Reproductive Endocrinology and Pathophysiology,3 Institute of Animal Reproduction and Food Research, PAS, Olsztyn 10-747, Poland Laboratory of Reproductive Endocrinology,4 Faculty of Agriculture, Okayama University, Tsushima Naka, Okayama 700-8530, Japan Department of Pharmacology,5 Faculty of Veterinary Medicine, Warmia and Mazury University in Olsztyn, Olsztyn 10-718, Poland

We have suggested in a previous in vitro study that tumor necrosis factor-{alpha} (TNF{alpha}) plays a role in the initiation of luteolysis in cattle. The aim of the present study was to examine the influence of different doses of TNF{alpha} on the estrous cycle in cattle by observing the standing behavior and measuring peripheral concentrations of progesterone (P4) during the estrous cycle. Moreover, we evaluated the secretion of P4, oxytocin (OT), nitric oxide (NO), and luteolytic (prostaglandin F2{alpha} [PGF2{alpha}] and leukotriene C4 [LTC4]) and luteotropic (PGE2) metabolites of arachidonic acid in peripheral blood plasma as parameters of TNF{alpha} actions. Mature Holstein/Polish black and white heifers (n = 36) were treated on Day 14 of the estrous cycle (Day 0 = estrus) by infusion into the aorta abdominalis of saline (n = 8), an analogue of PGF2{alpha} (cloprostenol, 100 µg; n = 3) or saline with TNF{alpha} at doses of 0.1 (n = 3), 1 (n = 8), 10 (n = 8), 25 (n = 3), or 50 µg (n = 3) per animal. Peripheral blood samples were collected frequently before, during, and up to 4 h after TNF{alpha} treatment. After Day 15 of the estrous cycle, blood was collected once daily until Day 22 following the first estrus. Lower doses of TNF{alpha} (0.1 and 1 µg) decreased the P4 level during the estrous cycle and consequently resulted in shortening of the estrous cycle (18.8 ± 0.9 and 18.0 ± 0.7 days, respectively) compared with the control (22.3 ± 0.3 days, P < 0.05). One microgram of TNF{alpha} increased the PGF2{alpha} (P < 0.001) and NO (P < 0.001) concentrations and decreased OT secretion (P < 0.01). Higher doses of TNF{alpha} (10, 25, 50 µg) stimulated synthesis of P4 (P < 0.001) and PGE2 (P < 0.001), inhibited LTC4 secreton (P < 0.05), and consequently resulted in prolongation of the estrous cycle (throughout 30 days, P < 0.05). Altogether, the results suggest that low concentrations of TNF{alpha} cause luteolysis, whereas high concentrations of TNF{alpha} activate corpus luteum function and prolong the estrous cycle in cattle.

1 This research was supported by the Grants-in Aid for Scientific Research (KBN 5P06K 003 21; JSPS 14360168) and Polish-Japanese Joint Research Project under the agreement between the Polish Academy of Sciences and the Japan Society for the Promotion of Sciences.

2 Correspondence: Dariusz J. Skarzynski, FAX: 48 89 524 03 47; skadar{at}pan.olsztyn.pl




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