Periconceptional Undernutrition in Sheep Affects Adult Phenotype Only in Males

Periconceptional undernutrition (PCUN) in sheep alters fetal growth and metabolism and postnatal growth regulation, but effects on adult body composition are unknown. We investigated the effects of PCUN on adult phenotype. Singleton lambs of ewes fed normally (N, n=17) or undernourished before (UN-61-0 d, n=23), before and after (UN-61-30 d, n=19), or after (UN-2-30d, n=17) mating (d0) were weighed at birth, 12 weeks, and intermittently to adulthood. At the age of 3-4 years, body composition was assessed by dual-emission X-ray absorptiometry followed by postmortem examination. Compared with N animals, male, but not female, offspring of all UN groups had greater % fat mass (all UN versus N: 9±1 versus 2±1%, P<0.001) and perirenal fat (544±36 versus 222±44 g, P=0.002), and proportionately smaller hearts (4.5±0.1 versus 5.2±0.2 g·kg−1), lungs (9.1±0.2 versus 10.6±0.5 g·kg−1), and adrenals (0.06±0.002 versus 0.08±0.003 g·kg−1). UN males also had larger testes (726±21 versus 545±32 g, P=0.007), but UN females had smaller ovaries (2.7±0.08 versus 3.4±0.4 g, P=0.01). Changes were independent of birth weight or postnatal growth velocity. Brief PCUN has sex-specific effects on adult phenotype, predominantly affecting males, which may contribute to adverse metabolic outcomes

Unpredictable feeding impairs glucose tolerance in growing lambs.

Irregular eating is associated with insulin resistance and metabolic disease in adults but may affect young, growing children differently. We investigated the metabolic effects of unpredictable feeding in female juvenile lambs randomly assigned to receive, for six weeks, maintenance feed given twice daily in equal portions (Control Group, C; n = 24) or the same weekly feed amount in aliquots of variable size at unpredictable times (Unpredictable Group, U; n = 21). Intravenous glucose tolerance tests (IVGTT), insulin tolerance tests (ITT), and measurement of diurnal plasma cortisol concentrations were performed pre and post the dietary intervention. Groups were compared using t test and RM ANOVA. Weight gain was similar in both groups (C 18 ± 2%; U 16 ± 2% of initial body weight). Glucose area under the curve (AUC) was unchanged in C (AUC pre 818 ± 34, post 801 ± 33 mmol.min.l(-1)), but increased by 20% in U (pre 830 ± 25, post 1010 ± 19 mmol.min.l(-1); p<0.0001), with an inadequate insulin response to glucose load (log(AUC insulin first 40 minutes) post intervention C 1.49 ± 0.04 vs U 1.36 ± 0.04 ng.min.ml(-1); p = 0.03). Insulin tolerance and diurnal variation of plasma cortisol concentrations were not different between groups. Unpredictable feeding impairs insulin response to glucose in growing lambs despite high quality food and normal weight gain. Irregular eating warrants investigation as a potentially remediable risk factor for disordered glucose metabolism

Short Communication Effects of periconceptional undernutrition on maternal taurine concentrations in sheep

Abstract Taurine has an important role in numerous physiological processes, including many aspects of fetal development such as development of the pancreas and brain, and requirements increase during pregnancy. Periconceptional undernutrition has long-term effects on pancreas and brain function of the offspring, but the effects on maternal taurine economy are unknown. We, therefore, studied the effects of different periods of periconceptional undernutrition on maternal plasma and urine taurine concentrations before and during pregnancy. Four groups of singleton-bearing ewes were studied (n 10-11): controls fed ad libitum, and groups undernourished from 60 d before until mating (PreC), from 2 d before mating until 30 d after mating (PostC) or from 60 d before until 30 d after mating (PreþPostC). In PreC ewes, plasma taurine concentrations remained at control levels for the first 30 d, and then decreased through the remainder of undernutrition, but recovered by 30 d after mating; urinary taurine excretion was low at mating, but recovered similarly. In PostC ewes, plasma taurine concentrations recovered after 2 weeks despite ongoing undernutrition; urinary taurine excretion had recovered by 30 d after mating. Preþ PostC ewes followed the same pattern as PreC for the first 60 d, but plasma taurine concentrations and urinary excretion recovered slowly, and did not reach the control levels until 97 d. These data suggest that different periods of mild periconceptional undernutrition in sheep have different but substantial effects on maternal taurine homoeostasis. These effects may be one mechanism by which maternal periconceptional undernutrition alters development of the offspring with implications for adult health

Effect of unpredictable feeding on diurnal cortisol concentrations.

<p>Diurnal plasma cortisol concentrations, before (A) and after (B) the six week dietary intervention in regularly fed (C) and unpredictably fed (U) sheep. Values are mean±SEM. There are no significant differences between groups. Solid lines parallel to the x axis reflect periods of darkness.</p

Do Alterations in placental 11β-hydroxysteroid dehydrogenase (11βHSD) activities explain differences in fetal hypothalamic-pituitary- adrenal (HPA) function following periconceptional undernutrition or twinning in sheep?

Periconceptional undernutrition (UN) in sheep accelerates fetal hypothalamic-pituitary-adrenal (HPA) axis activation, resulting in preterm birth. In contrast, twin conception suppresses fetal HPA function and delays prepartum HPA activation. We hypothesized that these dissimilar effects on fetal HPA activity result from different influences of maternal glucocorticoid (GC) on maturation of the fetal HPA axis, mediated via different activities of placental 11β-hydroxysteroid dehydrogenase (11βHSD) isozymes. We examined the effects of twinning and maternal periconceptional UN from 60 days before until 30 days after mating on the ontogeny of placental 11βHSD-1 and -2 enzyme activities. At day 85 of gestation, placental 11βHSD-2 activity was lower in UN than in normally nourished (N) fetuses (P <.05) and was higher in twins than in singletons (P <.05). Furthermore, placental 11βHSD-1 activity was not different between nutritional groups but was higher in twins than in singletons (P =.01). At day 85, fetal plasma cortisol (P <.001) and cortisone (P <.001) concentrations were lower in UN than in N fetuses, but the cortisol to cortisone ratio was higher in UN than in N fetuses (P =.01). There was no effect of fetus number on plasma cortisol or cortisone concentrations or on the ratio of cortisol to cortisone at day 85. Therefore, periconceptional UN and twinning may result in the alterations of placental 11βHSD isozyme activities at particular times during gestation. Changes in these activities during critical periods of fetal development could affect transplacental transfer or placental generation of GCs that reach the fetus, potentially influencing the timing of activation of the fetal HPA axis, fetal maturation, and hence the development and health later in life