Influence of Restricted Maternal Nutrition in Early to Mid Gestation on Placental and Fetal Development at Term in Sheep

Abstract

We investigated the influence of restricted maternal nutrition between 28 and 77 d of gestation on placental weight and appearance, and on fetal weight and conformation. Single-bearing ewes were fed either twice [i.e. controls (n = 19)] or half [i.e. nutrient-restricted (n = 28)] their energy requirements from 28 to 77 d of gestation, after which all ewes were fed to fully meet the energy requirements for maintenance and pregnancy. Close to term (145 +/- 1 d) placental weight was higher in the nutrient-restricted group [nutrient-restricted, 416.3 +/- 12.6 g; controls, 347.4 +/- 17.6 g (p < 0.01)], as was the abundance of everted placentomes. There was no significant difference in total fetal weight, or weights of individual organs between groups, but crown-rump length was significantly greater in lambs born to nutrient-restricted ewes [nutrient-restricted, 50.4 +/- 0.4 cm; controls, 48.2 +/- 0.6, cm (p < 0.01)]. Fetal to placental weight ratio was lower in the nutrient-restricted group [nutrient-restricted, 9.51 +/- 0.23; controls, 10.81 +/- 0.39 (p < 0.01)]. A stronger relationship between the total weight of the fetal component of the placental and fetal weight was observed in controls (r2 = 0.50) than in nutrient-restricted ewes (r2 = 0.18). In conclusion, maternal nutrient restriction over the period of rapid placental growth results in a larger placenta and altered placental to fetal weight ratio if ewes are subsequently fed to requirements for the remainder of gestation.

The differential effects of the timing of maternal nutrient restriction in the ovine placenta on glucocorticoid sensitivity, uncoupling protein 2, peroxisome proliferator-activated receptor-γ and cell proliferation

“…During maternal NR in sheep, maternal glucose concentrations are either unchanged (Edwards & McMillen 2001, Bispham et al 2003, Sosa et al 2009 or reduced (Heasman et al 1998a, Osgerby et al 2002, Quigley et al 2008, whereas plasma NEFA concentrations are consistently raised (Chandler et al 1985, Bauer et al 1995, Heasman et al 1998a, Brameld et al 2000, Bispham et al 2003, Quigley et al 2008, Sosa et al 2009). Fetal plasma NEFA concentrations, however, remain unchanged (Bauer et al 1995) as transfer of NEFA across the ovine placenta is limited (Hull et al 1979).…”

“…Previously, when nutrient-restricted sheep were subsequently fed to requirements from mid-gestation (80 days to term), the weights of the fetal component of the placenta, as well as that of the whole placenta weight, increased compared with adequately fed controls (Clarke et al 1998, Heasman et al 1998a. In the present study, we did not detect a difference in the total placental weight following NR at each of the different gestational windows but found a marked loss of cell proliferation throughout the placenta following maternal NR between days 66 and 110.…”

“…Maternal nutrient restriction (NR) during early-to-mid-gestation significantly affects placental growth and morphology (Clarke et al 1998, Heasman et al 1998a, causing a reduction in the weight of the fetal component of the placentome (Clarke et al 1998). At the same time placental sensitivity to glucocorticoids is raised in conjunction with reduced cell proliferation, downregulation of insulin-like growth factor (IGF)1 receptor gene expression while that of uncoupling protein (UCP)2 is upregulated (Gnanalingham et al 2007).…”

“…Following maternal NR, maternal glucose concentrations can be reduced (Heasman et al 1998a) and plasma non-esterified fatty acids (NEFA) increased (Heasman et al 1998a, Bispham et al 2003. While placental transfer of NEFA to the fetus in sheep is normally limited (Hull et al 1979), when nutrient supply is constrained they may play a role in placental metabolism in conjunction with increased uptake of ketone bodies (Chandler et al 1985).…”

Nutritional manipulation between early to mid-gestation: effects on uncoupling protein-2, glucocorticoid sensitivity, IGF-I receptor and cell proliferation but not apoptosis in the ovine placenta

“…During this period, maternal nutrient restriction (NR; i.e. w50%) has significant effects on placental growth and morphology (Clarke et al 1998, Heasman et al 1998 and causes a reduction in the mean weight of individual placentomes (Clarke et al 1998), but the mechanism mediating this response has not been established. These adaptations within the placenta occur in conjunction with a reduced potential capacity to inactivate maternal cortisol through the enzyme 11b-hydroxysteroid dehydrogenase (11bHSD) type 2 (Whorwood et al 2001), which itself may be in response to a decrease in maternal plasma cortisol (Bispham et al 2003).…”