Maternal Growth Hormone Treatment from Day 35 to 80 of Gestation Alters Nutrient Partitioning in Favor of Uteroplacental Growth in the Overnourished Adolescent Sheep1

Abstract

Overnourishing the pregnant adolescent ewe promotes maternal tissue synthesis at the expense of placental growth and leads to a major reduction in lamb birth weight at term. Growth hormone (GH) secretion is attenuated in these overnourished dams and the maternal somatotrophic axis may play a key role in coordinating nutrient usage in the pregnant adolescent. Thus we investigated whether increasing maternal GH during the period of rapid placental proliferation alters nutrient partitioning between the maternal, placental, and fetal tissues as assessed at Day 81 of gestation. Adolescent recipient ewes were implanted with singleton embryos, derived from superovulated dams and a single sire on Day 4 postestrus. Thereafter, the ewes were offered either a high (H) or moderate intake (M) of the same complete diet. From Day 35 to 80 of gestation, ewes were either injected twice daily (s.c. at 0800 and 1800 h) with recombinant bovine GH (bGH, 0.14 mg/kg live weight/day) or remained untreated (n = 8 ewes per group). Maternal concentrations of GH, insulin, insulin-like growth factor (IGF-1), glucose, and non-esterified fatty acids (NEFAs) were higher, and leptin secretion lower, in bGH-treated dams from both nutritional groups. Maternal body weight gain was higher in H versus M groups and was independent of bGH treatment. Treatment with bGH reduced relative perirenal and carcass fat deposition and increased carcass protein content in both H and M dams. Uteroplacental mass (uterus + placentomes + fetal membranes) averaged 1099, 1069, 1112, and 1754 g in M, H, M+GH, and H+GH groups. This significant increase in uteroplacental development in the H+GH group was associated with higher fetal kidney and liver weights and elevated fetal insulin, glucose, and lactate concentrations. Treatment with bGH also induced polyhydramnios in the H group. The transplacental glucose gradient was increased twofold in the H+GH group but placental GLUT- 1 and GLUT-3 expression was unaffected. In conclusion, administration of GH during the period of rapid placental proliferation alters endocrine status and thus nutrient partitioning in the overnourished adolescent dam in favor of uteroplacental and fetal growth. It remains to be established whether these effects are due wholly to alterations in maternal metabolism or if they also reflect an effect of bGH and/or the IGF system at the level of the uteroplacenta.

Fetoplacental growth and vascular development in overnourished adolescent sheep at day 50, 90 and 130 of gestation

“…This approach was critical to determine the basis of the previously observed changes in placental development and function in late gestation. The study demonstrated that placental mass per se is not perturbed by maternal overfeeding until sometime during the final third of pregnancy and as such confirms previous studies in which the pregnancies were terminated at single points coincident with either mid (Wallace et al 2004b or late (Wallace et al 2000(Wallace et al , 2002a(Wallace et al , 2002b gestation. Moreover, the data revealed for the first time that the fetuses of overnourished dams may be initially on a higher growth trajectory than control fetuses between day 50 and 90 of gestation, with fetal weight being 11% greater by day 90 in the H group.…”

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

“…The decrease in caruncle expression of IGFBP-1 can be attributed to two possible mechanisms. First, IGFBP-1 is inversely regulated by insulin (Suikkari et al 1989), and it has been shown previously that GH administration during gestation leads to hyperinsulinemia (Wallace et al 2004). Given that we achieved significant stimulation of IGF-I similar to that reported by Wallace et al one could reason that we generated a similar insulin response that reduced caruncle expression of IGFBP-1.…”

“…Wallace et al initiated GH administration to adolescent ewes at the appropriate time (day C D WRIGHT and others . GH effects on placental and fetal development 35); however, the GH treatment continued to day 80 (Wallace et al 2004), well past the reported cessation of oGH expression in the placenta (Lacroix et al 1996(Lacroix et al , 1999. Although Wallace et al reported an increase in placental weight in the over-nourished adolescent ewes with singletons; these ewes are predisposed to placental and fetal growth restriction due to the high plane of nutrition.…”

“…Wallace et al (2004) reported an increase in uteroplacental weight due to GH infusion from 35-80 dGA; however, this is due likely to increased fetal fluid weight resulting from polyhydraminios, as total and average placentome weights and fetal weights were not statistically different as a result of GH treatment. Furthermore, the increase in uteroplacental weight (Wallace et al 2004) was only seen in adolescent ewes maintained on a high dietary intake, a feeding regimen used in adolescent ewes to generate fetal growth restriction (Wallace et al 1997, Anthony et al 2003. More recently, treatment of ewes from 35-65 dGA with GH failed to alter fetal or placental development (Wallace et al 2006), as measured some 65 days later, and the GH was only administered to the high intake adolescent ewes.…”

“…Only endometrial gland proliferation was stimulated and this effect was seen with concurrent interferon-t administration (Spencer et al 1999). Wallace et al (2004) reported an increase in uteroplacental weight due to GH infusion from 35-80 dGA; however, this is due likely to increased fetal fluid weight resulting from polyhydraminios, as total and average placentome weights and fetal weights were not statistically different as a result of GH treatment. Furthermore, the increase in uteroplacental weight (Wallace et al 2004) was only seen in adolescent ewes maintained on a high dietary intake, a feeding regimen used in adolescent ewes to generate fetal growth restriction (Wallace et al 1997, Anthony et al 2003.…”