Periconceptional growth hormone treatment alters fetal growth and development in lambs

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.