Maternal periconceptional and first trimester protein restriction in beef heifers: effects on maternal performance and early fetal growth

This study evaluated the effect of protein restriction during the periconception (PERI) and first trimester (POST) periods on maternal performance, physiology and early fetal growth. Yearling nulliparous heifers (n = 360) were individually fed a diet high or low in protein (HPeri and LPeri respectively) beginning 60 days before conception. From 24 to 98 days post-conception (dpc), half of each treatment group changed to the alternative post-conception high- or low-protein diet (HPost and LPost respectively), yielding four groups in a 2 × 2 factorial design with a common diet until parturition. Protein restriction was associated with lower bodyweight subsequent to reduced (but positive) average daily weight gain (ADG) during the PERI and POST periods. During the POST period, ADG was greater in LPeri than HPeri heifers and tended to be greater in LPost than HPost heifers during the second and third trimester. Bodyweight was similar at term. The pregnancy rate did not differ, but embryo loss between 23 and 36 dpc tended to be greater in LPeri than HPeri heifers. Overall, a greater proportion of male fetuses was detected (at 60 dpc 63.3% male vs 36.7% female). Protein restriction altered maternal plasma urea, non-esterified fatty acids, progesterone, leptin and insulin-like growth factor 1 at critical stages of fetal development. However, profiles varied depending on the sex of the conceptus.Katrina J. Copping, Andrew Hoare, I. Caroline McMillen, Raymond J. Rodgers, Charles R. Wallace and Viv E.A. Perr

Periconception and first trimester diet modifies appetite, hypothalamic gene expression, and carcass traits in bulls

Nulliparous yearling beef heifers (n=360) were used to evaluate the effects of maternal dietary protein during the periconception and first trimester periods of gestation on postnatal growth, feedlot performance, carcass characteristics, and the expression of genes associated with appetite in the arcuate nucleus of their male progeny. Heifers were individually fed a diet of 1.18g crude protein (CP)/day High protein (HPeri) or 0.62g CP/day Low protein (LPeri) beginning 60days before conception. From 24 to 98days post-conception (dpc), half of each treatment group changed to the alternative post-conception diet and were fed 1.49g CP/day (HPost) or 0.88g CP/day (LPost) yielding four treatment groups in a 2×2 factorial design. From day 98 of gestation, heifers received a common diet until parturition. Calves were weaned at 183days and developed on pasture before feedlot entry. Bulls underwent a 70-day Residual Feed Intake (RFI) feedlot test commencing at 528days of age. Feedlot entry and final body weight (BW), feedlot average daily gain (ADG) and RFI were not different (p>0.05). Progeny of dams that had a change in diet (LPeri/HPost and HPeri/LPost) had 9% higher daily dry matter intake (DMI) during the RFI test (p<0.05) than progeny of dams that received low diet throughout both the peri-conception period and first trimester (LPeri/LPost). Further, mRNA expression of the appetite-stimulating agouti-related protein (AGRP) was increased in the arcuate nucleus of High Peri/LPost bulls (p<0.05). Longissimus dorsi muscle cross sectional area, carcass dressing percentage, and estimated retail beef yield (RBY) were all higher (p<0.05), and rump (P8) fat tended to be lower (p=0.07), for bulls from HPost dams despite no difference in carcass weight (p<0.05). This study is of commercial importance to the livestock industry as specific periods of maternal dietary supplementation may increase feed intake, enhance progeny muscling, and alter fat deposition leading to improvement in efficiency of meat production in beef cattle.Katrina J. Copping, Matthew J. Callaghan, Geert H. Geesink, Jessica R. Gugusheff, I. Caroline McMillen, Raymond J. Rodgers, Beverly S. Muhlhausler, Mini A. Vithayathil and Viv E. A. Perr

The reliance on α‐adrenergic receptor stimuli for blood pressure regulation in the chronically hypoxaemic fetus is not dependent on post‐ganglionic activation

Key points: Chronic hypoxaemia is associated with intrauterine growth restriction (IUGR) and a predisposition to the development of hypertension in adult life. IUGR fetuses exhibit a greater reliance on α-adrenergic activation for blood pressure regulation. The fetal blood pressure response to post-ganglionic blockade is not different between control and IUGR fetuses. The decrease in mean arterial pressure is greater in the IUGR sheep fetus after α-adrenergic receptor blockade at the level of the vasculature and this is inversely related to fetal urn:x-wiley:00223751:media:tjp14494:tjp14494-math-0001. The increased reliance that the IUGR fetus has on α-adrenergic activation for maintenance of mean arterial pressure is not a result of increased post-ganglionic sympathetic activation. Abstract: Intrauterine growth restriction (IUGR) is associated with an increased risk of cardiovascular disease in adult life. Placental restriction (PR) in sheep results in chronic hypoxaemia and early onset IUGR with increased circulating plasma noradrenaline concentrations. These IUGR fetuses exhibit a greater decrease in mean arterial pressure (MAP) during α-adrenergic blockade. We aimed to determine the role of post-ganglionic sympathetic activation with respect to regulating MAP in IUGR fetal sheep. PR was induced by carunclectomy surgery prior to conception. Fetal vascular catheterization was performed at 110–126 days gestational age (GA) (term, 150 days) in nine control and seven PR-IUGR fetuses. The fetal blood pressure response to both a post-ganglionic and an α-adrenergic receptor blocker was assessed at 116–120 days GA and/or 129–131 days GA. The effect of both post ganglionic and α-adrenergic blockade on fetal blood pressure was then compared between control and IUGR fetuses at both GAs. There was no difference in the effect of post-ganglionic blockade on MAP in control and IUGR fetal sheep at either 116–120 days GA or 129–131 days GA. α-adrenergic receptor blockade decreased MAP to the same extent in both control and IUGR fetuses at 116–120 days GA. At 129–131 days GA, the drop in MAP in response to α-adrenergic receptor blockade was greater in IUGR fetuses than controls. There was a significant inverse relationship between the drop in MAP in response to α-adrenergic receptor blockade at both GAs with fetal urn:x-wiley:00223751:media:tjp14494:tjp14494-math-0002. Thus, the increased dependence on α-adrenergic activation for blood pressure regulation in the chronically hypoxaemic IUGR fetus is not a result of increased post-ganglionic sympathetic activation.Jack R. T. Darby, Tamara J. Varcoe, Stacey L. Holman, I. Caroline McMillen, Janna L. Morriso

Cardiac growth and metabolism of the fetal sheep are not vulnerable to a 10 day increase in fetal glucose and insulin concentrations during late gestation

Aims: To evaluate the effects of fetal glucose infusion in late gestation on the mRNA expression and protein abundance of molecules involved in the regulation of cardiac growth and metabolism. Main methods: Either saline or glucose was infused into fetal sheep from 130 to 140 days (d) gestation (term, 150 d). At 140 d gestation, left ventricle tissue samples were collected. Quantitative real-time RT-PCR and Western blot were used to determine the mRNA expression and protein abundance of key signalling molecules within the left ventricle of the fetal heart. Key findings: Although intra-fetal glucose infusion increased fetal plasma glucose and insulin concentrations, there was no change in the expression of molecules within the signalling pathways that regulate proliferation, hypertrophy, apoptosis or fibrosis in the fetal heart. Cardiac Solute carrier family 2 member 1 (SLC2A1) mRNA expression was decreased by glucose infusion. Glucose infusion increased cardiac mRNA expression of both Peroxisome proliferator activated receptor alpha (PPARA) and peroxisome proliferator activated receptor gamma (PPARG). However, there was no change in the mRNA expression of PPAR cofactors or molecules with PPAR response elements. Furthermore, glucose infusion did not impact the protein abundance of the 5 oxidative phosphorylation complexes of the electron transport chain. Significance: Despite a 10-day doubling of fetal plasma glucose and insulin concentrations, the present study suggests that within the fetal left ventricle, the mRNA and protein expression of the signalling molecules involved in cardiac growth, development and metabolism are relatively unaffected.Jack R.T. Darby, Song Zhang, Stacey L. Holman, Beverly S. Muhlhausler, I. Caroline McMillen, Janna L. Morriso

Role of placenta: development and function

J.S. Robinson, I.C. McMillen, S. Fielke, L. Evans, F. Lok and J.A. Owen

Maternal periconceptional and first trimester protein restriction in beef heifers: effects on placental parameters and fetal and neonatal calf development

Few studies have investigated the effects of nutrition during the periconception and early gestation periods on fetal and placental development in cattle. In this study, nulliparous yearling heifers (n = 360) were individually fed a diet high or low in protein (HPeri and LPeri) beginning 60 days before conception. From 24 to 98 days after conception, half of each treatment group was changed to the alternative high- or low-protein diet (HPost and LPost) yielding four groups in a 2 × 2 factorial design. A subset of heifers (n = 46) was necropsied at 98 days after conception and fetoplacental development assessed. Placentome number and volume decreased in response to LPeri and LPost diets respectively. Absolute lung, pancreas, septum and ventricle weights decreased in LPost versus HPost fetuses, whereas the post-conception diet altered absolute and relative liver and brain weights depending on sex. Similarly, changes in fetal hepatic gene expression of factors regulating growth, glucose output and lipid metabolism were induced by protein restriction in a sex-specific manner. At term, neonatal calf and placental measures were not different. Protein restriction of heifers during the periconception and early gestation periods alters fetoplacental development and hepatic gene expression. These changes may contribute to functional consequences for progeny, but this may not be apparent from gross morphometry at birth.K. J. Copping, K. Hummitzsch, I. C. McMillen, J. L. Morrison, R. J. Rodgers and V. E. A. Perry ... et al

PPARgamma activation in late gestation does not promote surfactant maturation in the fetal sheep lung

Respiratory distress syndrome results from inadequate functional pulmonary surfactant and is a significant cause of mortality in preterm infants. Surfactant is essential for regulating alveolar interfacial surface tension, and its synthesis by Type II alveolar epithelial cells is stimulated by leptin produced by pulmonary lipofibroblasts upon activation by peroxisome proliferator-activated receptor γ (PPARγ). As it is unknown whether PPARγ stimulation or direct leptin administration can stimulate surfactant synthesis before birth, we examined the effect of continuous fetal administration of either the PPARγ agonist, rosiglitazone (RGZ; Study 1) or leptin (Study 2) on surfactant protein maturation in the late gestation fetal sheep lung. We measured mRNA expression of genes involved in surfactant maturation and showed that RGZ treatment reduced mRNA expression of LPCAT1 (surfactant phospholipid synthesis) and LAMP3 (marker for lamellar bodies), but did not alter mRNA expression of PPARγ, surfactant proteins (SFTP-A, -B, -C, and -D), PCYT1A (surfactant phospholipid synthesis), ABCA3 (phospholipid transportation), or the PPARγ target genes SPHK-1 and PAI-1. Leptin infusion significantly increased the expression of PPARγ and IGF2 and decreased the expression of SFTP-B. However, mRNA expression of the majority of genes involved in surfactant synthesis was not affected. These results suggest a potential decreased capacity for surfactant phospholipid and protein production in the fetal lung after RGZ and leptin administration, respectively. Therefore, targeting PPARγ may not be a feasible mechanistic approach to promote lung maturation.Jiaqi Ren, Mitchell C. Lock, Jack R.T. Darby, Sandra Orgeig, Stacey L. Holman, Megan Quinn, Mike Seed, Beverly S. Muhlhausler, I. Caroline McMillen and Janna L. Morriso