Effects of early gestation GH administration on placental and fetal development in sheep

Abstract

Ovine GH (oGH) is synthesized in placental tissue during maximal placental growth and development. Our objectives were to localize oGH mRNA in the placenta, and study the impact of exogenous GH on twin pregnancies during the normal window (35-55 days of gestational age; dGA) of placental expression. In situ hybridization localized oGH mRNA in uterine luminal epithelium but not in tissues of fetal origin. While maternal GH and IGF-I concentrations were increased (P!0 . 001) approximately tenfold, uterine, uterine fluid, placental, and fetal weights were unaffected by treatment at either 55 or 135 dGA. Fetal length, liver weight, and liver weight per kg of body weight were unaffected by maternal GH treatment. However, in the cotyledon, IGF-binding protein (BP)-1 and IGFBP-4 mRNA concentrations were increased (P!0 . 05), while IGFBP-2 mRNA was decreased (P!0 . 05).The concentration of mRNA for IGFBP-3 was unaffected by treatment. Within the caruncle, IGFBP-1 mRNA was decreased (P!0 . 05), while IGFBP-3 and IGFBP-4 mRNA were increased (P!0 . 05), and IGFBP-2 mRNA was unchanged due to GH treatment. While our data indicate that elevated maternal GH and IGF-I concentrations during early and mid-gestation do not enhance placental and fetal growth in twin pregnancies, localization of GH mRNA in uterine luminal epithelium could explain GHs transitory expression from 35 to 55 dGA, since by the end of this period the majority of the uterine luminal epithelium has fused with chorionic binucleate cells forming the placental syncytium.

Effects of overfeeding naturally-mated adolescent ewes on maternal, fetal, and postnatal lamb growth1

“…2 by methods previously described by this laboratory (Warren et al, 1990;Kappes et al, 1992). The tcRNA was subjected to quantitative real-time reverse transcriptase-PCR (qPCR) analysis, as previously described (Erikson-Hagen et al, 2005;Wright et al, 2008). Briefl y, the primer sets listed in Table 2 were used to generate intron-spanning cDNA amplicons for sheep IGF1, IGF2, IGF1 receptor (IGF1R), IGF2 receptor (IGF2R), insulin receptor (INSR), and ribosomal protein subunit 15 (RPS15), which were sequenced to verify authenticity and used to generate standard curves spanning from 10 to 1 × 10 6 pg starting quantity.…”

“…After 40 cycles of qPCR, with a fl uorescence measurement after each cycle, a melting curve analysis was initiated at 55ºC, with fl uorescence measured at 0.5°C increments until 95°C. Relative expression of IGF1, IGF2, IGF1R, IGF2R, and INSR was determined by dividing the starting quantity of the mRNA of interest by the starting quantity of RPS15 (Erikson-Hagen., 2005;Wright et al, 2008).…”

The neglected role of insulin‐like growth factors in the maternal circulation regulating fetal growth

“…However, in later pregnancy, increasing maternal circulating IGF‐I appears to have no immediate effect on maternal body composition or fetal weight (Harding et al 1997). The extent of IGF‐I actions on the mother is dependent on gestational age, maternal age and nutrition, and whether the pregnancy is a singleton or twin (Table 1: Costine et al 2005; Wallace et al 2006 a ; Kenyon et al 2007; Wright et al 2008; Koch et al 2010). Like the pig, maternal IGF‐I may have most benefit on ovine fetal growth in adverse maternal environments.…”

Periconceptional growth hormone treatment alters fetal growth and development in lambs1

“…Administration of GH daily at 0.2 mg/kg from d 35 to 55 had no effect on fetal weight by the end of treatment and did not affect fetal weight at d 135 of gestation (Wright et al, 2008). We interpret this to mean that whatever programming effect GH treatment has during very early gestation, the window of opportunity to impart that program is no longer open by as early as d 35 of gestation.…”

“…We interpret this to mean that whatever programming effect GH treatment has during very early gestation, the window of opportunity to impart that program is no longer open by as early as d 35 of gestation. Wright et al (2008) chose d 35 to 55 to administer GH because this is the period of gestation in which the placenta is producing GH. However, increases in maternal pituitary GH or peripheral IGF-I during the first 4 wk of gestation may be more critical to affecting the growth of the fetoplacental unit than the GH produced for 20 d by the endometrium during wk 5 to 8 of gestation.…”