Periconceptional treatment with growth hormone alters fetal growth and development in sheep.

摘要

Altering the fetal environment can modify the composition or growth rate of the fetus, a concept known as fetal programming. A majority of the research in this area has focused on intrauterine growth restriction (IUGR), which has been linked to adult diseases. A few studies have attempted to ameliorate the negative effects of IUGR, by applying growth promoters late in gestation, and have only observed transient effects. Our laboratory has previously shown that growth hormone (GH) treatment around the time of breeding alters the uterine environment early in gestation and results in larger lambs at birth. Therefore there were three main objectives investigated in the current work, each encompassing a different period of gestation. The first objective was to examine how a periconceptional injection of GH alters the uterine environment at the time of early embryonic development and if the trophectoderm to inner cell mass ratio is altered by treatment. The second objective was to determine how GH treatment may program nutrient transport in the placenta late in gestation. The third objective was to examine how a periconceptional injection of GH alters fetal growth and development at birth and how the GH axis may be altered in lambs born to ewes treated with GH. Periconceptional GH treatment altered the concentration of growth factors in uterine luminal fluid including TGF-beta1, insulin like growth factor-I and urea, but did not alter the ratio of trophectoderm to inner cell mass cells or the total number of blastomeres. Treatment with GH appeared to alter the placental expression of some nutrient transporters during gestation. Periconceptional treatment with growth hormone appears to alter the uterine environment during embryonic development, programming the cells of the embryo to exhibit an altered physiology. Periconceptional GH treatment increased lamb weight and abdominal girth. Lambs born to ewes treated with GH also had an altered GH axis as determined by a reduced hepatic expression of both insulin like growth factor-I and growth hormone receptor at birth and an altered response to GH releasing hormone challenge at 100 days of age. Periconceptional GH appears to program embryonic cells which develop into a more efficient placenta allowing for an increase in nutrient availability, ultimately leading to larger lambs at birth with an altered composition and an altered growth hormone axis.