Chen Yizhen, Green Jonathan A, Antoniou Eric, Ealy Alan D, Mathialagan Nagappan, Walker Angela M, Avalle Mary P, Rosenfeld Cheryl S, Hearne Leonard B, Roberts R Michael
Department of Animal Sciences, University of Missouri, Columbia, 65211, USA.
Endocrinology. 2006 May;147(5):2127-37. doi: 10.1210/en.2005-1310. Epub 2006 Feb 9.
In ruminants, conceptus interferon-tau (IFNT) alters maternal physiology to accommodate a pregnancy. We hypothesized that the effectiveness of IFNT on extending corpus luteum (CL) life span in nonpregnant ewes would depend upon the dose and manner of administration and would be correlated with the response in gene expression in endometrium. We anticipated that IFNT, whether administered im or by uterine infusion, would mimic changes observed in pregnancy. Ewes were assigned to five treatments: 1) uterine infusion of saline; 2) uterine infusion of ovine IFNT4 (200 microg/d); 3) saline im injection; 4) im injection of IFNT4 at low dose (200 microg/d); and 5) high dose (2 mg/d). CL life span was increased in groups 2 and 5, but not in 1, 3, and 4. Endometrial RNA extracted from groups 1-5 on d 14 and from d 14 pregnant and nonbred (cyclic) ewes was used to assess expression of 70 genes on microarrays. When pregnant and cyclic ewes were compared, 30 genes were up-regulated and nine down-regulated during pregnancy. Responses were slightly less in groups 2 and 5 but were much lower in group 4. The majority of the highly up-regulated genes were associated with antiviral responses. Those down-regulated included ones for IGF-II, hypoxia-inducible factor 1alpha, oxytocin receptor, prostaglandin F synthase, and cyclooxygenase-2. Quantitative PCR for selected genes confirmed these data and revealed that similar gene expression changes occurred in the CL of pregnant and group 2 ewes. IFNT treatment mimics pregnancy, but relatively high doses of im-injected IFNT are required to elicit a full endometrial response.
在反刍动物中，孕体干扰素-τ（IFNT）会改变母体生理机能以适应妊娠。我们推测，IFNT对未孕母羊黄体（CL）寿命延长的有效性将取决于给药剂量和方式，并且与子宫内膜基因表达的反应相关。我们预期，无论IFNT是通过肌肉注射还是子宫灌注给药，都会模拟妊娠时观察到的变化。将母羊分为五种处理组：1）子宫灌注生理盐水；2）子宫灌注绵羊IFNT4（200微克/天）；3）生理盐水肌肉注射；4）低剂量（200微克/天）肌肉注射IFNT4；5）高剂量（2毫克/天）。第2组和第5组的CL寿命延长，但第1、3和4组未延长。从第14天的第1 - 5组以及第14天的妊娠和未配种（周期发情）母羊中提取子宫内膜RNA，用于在微阵列上评估70个基因的表达。当比较妊娠母羊和周期发情母羊时，妊娠期间有30个基因上调，9个基因下调。第2组和第5组的反应略小，但第4组的反应要低得多。大多数高度上调的基因与抗病毒反应相关。下调的基因包括胰岛素样生长因子-II、缺氧诱导因子1α、催产素受体、前列腺素F合酶和环氧化酶-2的基因。对选定基因的定量PCR证实了这些数据，并揭示在妊娠母羊和第2组母羊的CL中发生了类似的基因表达变化。IFNT治疗模拟了妊娠，但需要相对高剂量的肌肉注射IFNT才能引发完整的子宫内膜反应。
