Different effects of maternal parity, cold exposure and nutrient restriction in late pregnancy on the abundance of mitochondrial proteins in the kidney, liver and lung of postnatal sheep

Abstract

Adaptation to the extrauterine environment at birth relies upon the onset of postnatal function and increased metabolism in the lungs, liver and kidney, mediated partly by activation of mitochondrial proteins such as the voltage-dependent anion channel (VDAC), cytochrome c and, in the lung only, uncoupling protein (UCP)2. The magnitude of adaptation is dependent on the maternal metabolic and endocrine environment. We, therefore, examined the influence of maternal cold exposure (MCE) induced by winter shearing of pregnant sheep in conjunction with nutrient restriction (NR; 50% reduction in maternal food intake from 110 days gestation up to term). The effect of parity was also examined, as the offspring of nulliparous mothers are growth restricted compared with multiparous offspring. All sheep were twin bearing. One twin was sampled after birth and its sibling at 30 days. In the lung, both MCE and maternal nulliparity enhanced UCP2 abundance. However, whilst VDAC abundance was decreased in both the offspring of nulliparous mothers and by NR, it was transiently raised by MCE. Kidney VDAC abundance was reduced by MCE and nulliparity, adaptations only influenced by NR in multiparous mothers. Cytochrome c abundance was raised by MCE and by NR in multiparous controls and raised in offspring of nulliparous mothers. Liver VDAC and cytochrome c abundance were transiently reduced by MCE and persistently lower in offspring of nulliparous mothers. In conclusion, changes in the maternal metabolic environment have marked tissue-specific effects on mitochondrial protein abundance in the lungs, liver and kidney that may be important in enabling the newborn to effectively adapt to the extrauterine environment.

Ontogeny and nutritional programming of mitochondrial proteins in the ovine kidney, liver and lung

“…These adaptations are likely to be mediated, in part, by the marked increase in circulating plasma cortisol (Fowden et al 1998) which has a pivotal role in enabling the newborn to effectively adapt to the extrauterine environment (Clarke et al 1998). What is notable about the ontogenic responses observed is the magnitude of changes in mitochondrial protein abundance between each tissue that may be related to the specificity of location for both VDAC and cytochrome c (Yakubu et al 2007) and the extent to which these are sensitive to maternal nutrient restriction. In this regard, there is a clear divergence in the timing as well as magnitude of mitochondrial adaptation within the kidney, liver and lung that is unrelated to tissue weight.…”

“…During the neonatal period, as the animal commences liquid feeding, there is a rise in solute turnover within the body that places substantial metabolic demands on the kidney, and this is met, in part, by increased mitochondrial activity. We have established that both VDAC and cytochrome c are located around the kidney tubules (Yakubu et al 2007) and would be expected to regulate fluid exchange. The decrease in the relative abundance of both mitochondrial proteins between 1 and 6 months of age occurs over a period when kidney growth continues but its mitochondrial content remains unchanged.…”

“…VDAC is located within the epithelial lining (Yakubu et al 2007) and may have a role in regulating gluconeogenesis (Lemasters & Holmuhamedov 2006). The rise in both VDAC and GR through gestation to peak after birth would, thus, coincide with the onset of glucose production around the time of birth (Fowden et al 1998), thereby promoting energy production by the liver.…”

“…VDAC is located in the outer mitochondrial membrane (Colombini 1979) and may be responsible for the release of cytochrome c from the inter-membrane space, one process that has been implicated in the chain of events culminating in apoptosis (Crompton 1999). Both of these mitochondrial proteins are highly abundant in the kidney, liver and lung of the newborn sheep (Yakubu et al 2007). They do, however, have tissue-specific locations that may explain their potentially very different functions between organs (Yakubu et al 2007).…”

“…Both of these mitochondrial proteins are highly abundant in the kidney, liver and lung of the newborn sheep (Yakubu et al 2007). They do, however, have tissue-specific locations that may explain their potentially very different functions between organs (Yakubu et al 2007). In the kidney, both VDAC and cytochrome c are located within the tubules, in the liver each is present within the epithelial lining, whereas, in the lung, VDAC is located in the alveoli and cytochrome c in the bronchioles.…”