Ott T L, Fleming J G, Spencer T E, Joyce M M, Chen P, Green C N, Zhu D, Welsh T H, Harms P G, Bazer F W
Department of Animal Science, Center for Animal Biotechnology, Institute of Biosciences and Technology, Texas A&M University, College Station 77843-2471, USA.
Biol Reprod. 1997 Sep;57(3):621-9. doi: 10.1095/biolreprod57.3.621.
Interferon tau (IFN tau) is the conceptus-produced antiluteolytic signal in ruminants. Three experiments examined the effects of s.c. administration of recombinant ovine (ro)IFN tau on interestrous interval (IEI), oxytocin (OT)-induced uterine prostaglandin F2alpha metabolite (PGFM) production, rectal temperature (RT), respiration rate (RR), and plasma concentrations of progesterone, cortisol, LH, and antiviral activity (AVA) in plasma and uterine flushings. In experiment I, 20 ewes were treated s.c. with either 0, 1, 2, or 4 mg/day roIFN tau (0.7 x 10(8) U/mg; 5 ewes/dosage) from Days 11 to 15 of the estrous cycle (estrus = Day 0) and were challenged with OT (30 IU) on Day 15. Jugular blood samples were collected at -10, 0, 10, 20, 30, 40, 50, and 60 min relative to the OT challenge and assayed for PGFM. Recombinant oIFN tau increased IEI (16.7, 18.7, and 22.6 +/- 0.6 days for 0, 2, and 4 mg roIFN tau, respectively, p < 0.01). Recombinant oIFN tau did not affect peak PGFM response to OT (2309 +/- 172 pg/ml; p > 0.1). However, the 4 mg/day dosage delayed the time to peak PGFM (32.4 vs. 47.5 +/- 3.4 min; p < 0.01, 0 vs. 4 mg) and resulted in approximately 200% higher concentrations of PGFM at 60 min post-OT (0 vs. 4 mg/day, p < 0.07). Experiment II was similar to experiment I, except that only the 0- and 4-mg/day dosages of roIFN tau were administered. Ewes were hysterectomized on Day 16, and assay of uterine flushes detected no AVA from ewes treated with either 0 or 4 mg/day roIFN tau. In experiment III, 20 ewes were treated s.c. with either 0, 2, 4, or 6 mg roIFN tau on Day 12. Blood samples, RT, and RR were obtained at frequent intervals for 24 h, and plasma was assayed for progesterone, cortisol, LH, and AVA. Plasma AVA, which increased in a dose-dependent manner, was detectable within 60 min and remained elevated at 24 h compared to control values. RT (elevated 0.5-1.0 degrees C), RR, and cortisol increased in response to all dosages of roIFN tau, with peak values occurring 150-180 min postinjection. For all dosages of roIFN tau, plasma progesterone declined from 120 to 360 min posttreatment and then returned to pretreatment values by 24 h (p < 0.01) as compared to controls. Overall, exogenous roIFN tau altered uterine PGFM response to OT from a pulse to a gradual and sustained elevation and extended IEI with only a transient decline in progesterone and mild hyperthermia, effects that are not expected to compromise pregnancy.
干扰素τ（IFNτ）是反刍动物胚胎产生的抗黄体溶解信号。三项实验研究了皮下注射重组羊（ro）IFNτ对发情间期（IEI）、催产素（OT）诱导的子宫前列腺素F2α代谢物（PGFM）产生、直肠温度（RT）、呼吸频率（RR）以及血浆和子宫冲洗液中孕酮、皮质醇、促黄体生成素（LH）和抗病毒活性（AVA）的影响。在实验I中，20只母羊在发情周期的第11至15天（发情日=第0天）皮下分别注射0、1、2或4mg/天的roIFNτ（0.7×10⁸U/mg；每个剂量5只母羊），并在第15天用OT（30IU）进行刺激。在OT刺激后-10、0、10、20、30、40、50和60分钟采集颈静脉血样并检测PGFM。重组oIFNτ延长了IEI（0、2和4mg roIFNτ组的IEI分别为16.7、18.7和22.6±0.6天，p<0.01）。重组oIFNτ不影响PGFM对OT的峰值反应（2309±172pg/ml；p>0.1）。然而，4mg/天的剂量延迟了PGFM达到峰值的时间（32.4分钟对47.5±3.4分钟；p<0.01，0mg对4mg），并导致OT注射后60分钟时PGFM浓度升高约200%（0mg/天对4mg/天，p<0.07）。实验II与实验I相似，只是仅给予0和4mg/天剂量的roIFNτ。母羊在第16天进行子宫切除，对子宫冲洗液的检测未发现0或4mg/天roIFNτ处理的母羊有AVA。在实验III中，20只母羊在第12天皮下注射0、2、4或6mg roIFNτ。在24小时内频繁采集血样、测量RT和RR，并检测血浆中的孕酮、皮质醇、LH和AVA。血浆AVA呈剂量依赖性增加，在60分钟内即可检测到，与对照值相比，在24小时时仍保持升高。所有剂量的roIFNτ均可使RT（升高0.5 - 1.0℃）、RR和皮质醇升高，峰值出现在注射后150 - 180分钟。对于所有剂量的roIFNτ，血浆孕酮在治疗后120至360分钟下降，然后在24小时时恢复到治疗前水平（p<0.01），与对照组相比。总体而言，外源性roIFNτ改变了子宫PGFM对OT的反应，使其从脉冲式升高变为逐渐持续升高，并延长了IEI，同时仅使孕酮短暂下降和出现轻度体温升高，这些影响预计不会对妊娠造成损害。
