Skarzynski Dariusz J, Bah Mamadou M, Deptula Katarzyna M, Woclawek-Potocka Izabela, Korzekwa Anna, Shibaya Masami, Pilawski Wojciech, Okuda Kiyoshi
Division of Reproductive Endocrinology and Pathophysiology, Institute of Animal Reproduction and Food Research, PAS, Olsztyn 10-747, Poland.
Biol Reprod. 2003 Dec;69(6):1907-13. doi: 10.1095/biolreprod.103.016212. Epub 2003 Aug 6.
We have suggested in a previous in vitro study that tumor necrosis factor-alpha (TNFalpha) 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 TNFalpha 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 F2alpha [PGF2alpha] and leukotriene C4 [LTC4]) and luteotropic (PGE2) metabolites of arachidonic acid in peripheral blood plasma as parameters of TNFalpha 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 PGF2alpha (cloprostenol, 100 microg; n = 3) or saline with TNFalpha at doses of 0.1 (n = 3), 1 (n = 8), 10 (n = 8), 25 (n = 3), or 50 microg (n = 3) per animal. Peripheral blood samples were collected frequently before, during, and up to 4 h after TNFalpha treatment. After Day 15 of the estrous cycle, blood was collected once daily until Day 22 following the first estrus. Lower doses of TNFalpha (0.1 and 1 microg) 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 TNFalpha increased the PGF2alpha (P < 0.001) and NO (P < 0.001) concentrations and decreased OT secretion (P < 0.01). Higher doses of TNFalpha (10, 25, 50 microg) 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 TNFalpha cause luteolysis, whereas high concentrations of TNFalpha activate corpus luteum function and prolong the estrous cycle in cattle.
我们在之前的一项体外研究中提出，肿瘤坏死因子-α（TNFα）在牛黄体溶解的起始过程中发挥作用。本研究的目的是通过观察发情周期中的站立行为并测量外周孕酮（P4）浓度，来研究不同剂量的TNFα对牛发情周期的影响。此外，我们评估了外周血浆中P4、催产素（OT）、一氧化氮（NO）以及花生四烯酸的黄体溶解（前列腺素F2α [PGF2α]和白三烯C4 [LTC4]）和黄体生成（前列腺素E2）代谢产物的分泌情况，将其作为TNFα作用的参数。在发情周期的第14天（第0天 = 发情），对36头成熟的荷斯坦/波兰黑白花小母牛进行处理，通过向腹主动脉注入生理盐水（n = 8）、PGF2α类似物（氯前列醇，100微克；n = 3）或含不同剂量TNFα的生理盐水，每头动物的剂量分别为0.1（n = 3）、1（n = 8）、10（n = 8）、25（n = 3）或50微克（n = 3）。在TNFα处理前、处理期间以及处理后长达4小时频繁采集外周血样。发情周期第15天后，每天采集一次血样，直至首次发情后的第22天。较低剂量的TNFα（0.1和1微克）在发情周期中降低了P4水平，因此与对照组（22.3 ± 0.3天）相比，导致发情周期缩短（分别为18.8 ± 0.9天和18.0 ± 0.7天，P < 0.05）。1微克的TNFα增加了PGF2α（P < 0.001）和NO（P < 0.001）的浓度，并降低了OT分泌（P < 0.01）。较高剂量的TNFα（10、25、50微克）刺激了P4（P < 0.001）和PGE2（P < 0.001）的合成，抑制了LTC4分泌（P < 0.05），因此导致发情周期延长（长达30天，P < 0.05）。总之，结果表明低浓度的TNFα会导致黄体溶解，而高浓度的TNFα会激活黄体功能并延长牛的发情周期。
