Division of Animal and Nutritional Sciences, Davis College of Agriculture, Natural Resources and Design, West Virginia University, Morgantown 26506, USA.
J Anim Sci. 2010 May;88(5):1619-25. doi: 10.2527/jas.2009-2392. Epub 2010 Jan 29.
Research in the area of fetal programming has focused on intrauterine growth restriction. Few studies have attempted to examine programming mechanisms that ultimately lead to lambs with a greater potential for postnatal growth. We previously demonstrated that treatment of ewes with GH at the time of breeding led to an increase in birth weight. Therefore, the objective of this study was to determine the effects of a single injection of sustained-release GH given during the periconceptional period on fetal growth and development and to determine if the GH axis would be altered in these offspring. Estrus was synchronized using 2 injections of PGF(2alpha); at the time of the second injection, ewes assigned to treatment were also given an injection of sustained-release GH. A maternal jugular vein sample was taken weekly to analyze IGF-I as a proxy for GH to estimate the duration of the treatment effect. In ewes treated with GH, IGF-I increased (P < 0.05) by wk 1 and remained elevated until wk 4 postinjection. Lambs were weighed, crown-rump length and abdominal girth were determined, and a plasma sample was collected. In a subset of male lambs, liver, heart, and brain weights were obtained, as well as left and right ventricular wall thicknesses. On postnatal d 100, a subset of ewe lambs were weighed and challenged with an intravenous injection of GHRH. Lambs from treated ewes had increased (P < 0.05) birth weight and abdominal girth compared with control lambs; however, there was no difference in crown-rump length. Expression of GH receptor and IGF-I were increased (P < 0.05) in lambs gestated by GH-treated ewes compared with control ewes. The left ventricular wall was thinner (P < 0.05) from lambs in the GH-treated group compared with control lambs. On postnatal d 100, those ewe lambs born to ewes treated with GH continued to be heavier (P < 0.05) and had no IGF-I response to GHRH challenge. In conclusion, treating ewes with a single injection of GH appeared to alter fetal growth and development. Lambs born to ewes treated with GH were larger at birth and had altered organ development, which may indicate that early maternal GH treatment may lead to permanent changes in the developing fetus. The ewe lambs maintained their growth performance to at least 100 d of postnatal life and appeared to have an altered GH axis, as demonstrated by the altered response to GHRH.
胎儿编程领域的研究集中在宫内生长受限上。很少有研究试图研究最终导致羔羊具有更大出生后生长潜力的编程机制。我们之前的研究表明，在配种时用 GH 治疗母羊会导致出生体重增加。因此，本研究的目的是确定在围孕期单次注射缓释 GH 对胎儿生长和发育的影响，并确定这些后代的 GH 轴是否会发生改变。使用 2 次 PGF(2alpha)注射同步发情；在第二次注射时，分配到治疗组的母羊也接受了缓释 GH 注射。每周从母羊颈静脉取一次样本，分析 IGF-I 作为 GH 的替代物，以估计治疗效果的持续时间。在接受 GH 治疗的母羊中，IGF-I 在第 1 周增加（P<0.05），并在注射后第 4 周一直升高。称重羔羊，测量头臀长和腹围，并采集血浆样本。在部分雄性羔羊中，还测量了肝脏、心脏和大脑的重量，以及左右心室壁的厚度。在产后 100 天，部分母羊羔羊称重，并接受 GHRH 静脉注射挑战。与对照羔羊相比，来自接受治疗的母羊的羔羊出生体重和腹围增加（P<0.05）；然而，头臀长没有差异。与对照母羊相比，来自接受 GH 治疗的母羊孕育的羔羊的 GH 受体和 IGF-I 的表达增加（P<0.05）。与对照组羔羊相比，GH 治疗组的左心室壁较薄（P<0.05）。在产后 100 天，那些来自接受 GH 治疗的母羊的母羊羔羊仍然更重（P<0.05），并且对 GHRH 挑战没有 IGF-I 反应。总之，给母羊单次注射 GH 似乎改变了胎儿的生长和发育。出生时来自接受 GH 治疗的母羊的羔羊更大，器官发育也发生了改变，这可能表明早期的母体 GH 治疗可能导致发育中的胎儿发生永久性变化。母羊羔羊至少在产后 100 天保持其生长性能，并表现出改变的 GH 轴，这表明对 GHRH 的反应改变。
