Roles of Tumor Necrosis Factor-α of the Estrous Cycle in Cattle: An In Vivo Study

Dariusz J. Skarzynski, Mamadou M. Bah, Katarzyna M. Deptula, Izabela Woclawek-Potocka, Anna Korzekwa, Masami Shibaya, Wojciech Pilawski, Kiyoshi Okuda

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We have suggested in a previous in vitro study that tumor necrosis factor-α (TNFα) 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 TNFα 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 F [PGF ] and leukotriene C4 [LTC4]) and luteotropic (PGE2) metabolites of arachidonic acid in peripheral blood plasma as parameters of TNFα 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 PGF (cloprostenol, 100 μg; n = 3) or saline with TNFα 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 TNFα treatment. After Day 15 of the estrous cycle, blood was collected once daily until Day 22 following the first estrus. Lower doses of TNFα (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 TNFα increased the PGF (P < 0.001) and NO (P < 0.001) concentrations and decreased OT secretion (P < 0.01). Higher doses of TNFα (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 TNFα cause luteolysis, whereas high concentrations of TNFα activate corpus luteum function and prolong the estrous cycle in cattle.

Original languageEnglish
Pages (from-to)1907-1913
Number of pages7
JournalBiology of reproduction
Issue number6
Publication statusPublished - Dec 2003


  • Corpus luteum function
  • Cytokines
  • Female reproductive tract
  • Ovulatory cycle
  • Uterus

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology


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