scholarly journals Maternal nutrient restriction in late pregnancy programs postnatal metabolism and pituitary development in beef heifers

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249924
Author(s):  
John M. Long ◽  
Levi A. Trubenbach ◽  
Kenneth C. Hobbs ◽  
Andrew E. Poletti ◽  
Chelsie B. Steinhauser ◽  
...  

Maternal undernutrition during pregnancy followed by ad libitum access to nutrients during postnatal life induces postnatal metabolic disruptions in multiple species. Therefore, an experiment was conducted to evaluate postnatal growth, metabolism, and development of beef heifers exposed to late gestation maternal nutrient restriction. Pregnancies were generated via transfer of in vitro embryos produced using X-bearing sperm from a single Angus sire. Pregnant dams were randomly assigned to receive either 100% (control; n = 9) or 70% (restricted; n = 9) of their total energy requirements from gestational day 158 to parturition. From post-natal day (PND) 301 until slaughter (PND485), heifers were individually fed ad libitum in a Calan gate facility. Calves from restricted dams were lighter than controls at birth (P<0.05) through PND70 (P<0.05) with no difference in body weight from PND105 through PND485 (P>0.10). To assess pancreatic function, glucose tolerance tests were performed on PND315 and PND482 and a diet effect was seen with glucose area under the curve being greater (P<0.05) in calves born to restricted dams compared to controls. At slaughter, total internal fat was greater (P<0.05) in heifers born to restricted dams, while whole pituitary weight was lighter (P<0.05). Heifers from restricted dams had fewer growth hormone-positive cells (somatotrophs) compared to controls (P<0.05). Results demonstrate an impaired ability to clear peripheral glucose in heifers born to restricted dams leading to increased deposition of internal fat. A reduction in the number of somatotrophs may contribute to the adipogenic phenotype of heifers born to restricted dams due to growth hormone’s known anabolic roles in growth, lipolysis, and pancreatic islet function.

2007 ◽  
Vol 292 (1) ◽  
pp. E32-E39 ◽  
Author(s):  
Kirsten R. Poore ◽  
Jane K. Cleal ◽  
James P. Newman ◽  
Julian P. Boullin ◽  
David E. Noakes ◽  
...  

The early-life environment has implications for risk of adult-onset diseases, such as glucose intolerance, insulin insensitivity, and obesity, effects that may occur with or without reduced birth weight. We determined the consequences of nutrient restriction in early gestation and early postnatal life and their interactions on postnatal growth, body composition, and glucose handling. Ewes received 100% (C, n = 39) or 50% nutritional requirements (U, n = 41) from 1 to 31 days gestation and 100% thereafter. Male and female offspring (singleton/twin) from C and U ewes were then fed either ad libitum (CC n = 22, UC n = 19) or to reduce body weight to 85% of target from 12 to 25 wk of age (CU n = 17, UU n = 22) and ad libitum thereafter. At 1.5 and 2.5 yr, glucose handling was determined by area under the curve (AUC) for glucose and insulin concentrations following intravenous glucose (0.5 g/kg body wt). Insulin sensitivity was determined at 2.5 yr following intravenous insulin (0.5 IU/kg). In females, postnatal undernutrition reduced ( P < 0.05) glucose AUC at both ages, regardless of prenatal nutrition. Postnatal undernutrition did not affect insulin secretion in females but enhanced insulin-induced glucose disappearance in singletons. Poor early postnatal growth was associated with increased fat in females. In males, glucose tolerance was unaffected by undernutrition despite changes in insulin AUC dependent on age, treatment, and single/twin birth. Nutrition in early postnatal life has long-lasting, sex-specific effects on glucose handling in sheep, likely due, in females, to enhanced insulin sensitivity. Improved glucose utilization may aid weight recovery but have negative implications for glucose homeostasis and body composition over the longer term.


2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 45-46
Author(s):  
Lindsey G Wichman ◽  
Colby A Redifer ◽  
Shelby L Davies ◽  
Allison M Meyer

Abstract We hypothesized that late gestational nutrient restriction (NR) would reduce colostrum yield and impair offspring transition to postnatal life. Primiparous, fall-calving crossbred beef heifers (BW: 451 ± 28 [SD] kg; BCS: 5.4 ± 0.7) were individually-fed either 100% (control; CON; n = 12) or 70% (n = 13) of NASEM net energy and metabolizable protein requirements for maintenance, pregnancy, and growth from d 160 of gestation to parturition. Delivery duration was determined as minutes from first fetal feet expulsion to birth. Calves were reared naturally by their dams and monitored for times from birth to first sternal recumbency, attempt to stand, and stand; vigor scores (1 = very weak, 5 = extremely vigorous) were assigned at 2, 5, 10, and 20 min of age. Total colostrum from one rear quarter was collected pre-suckling. Calf rectal temperatures were recorded at 0, 6, 12, 24, and 48 h postnatally. Data were analyzed with the fixed effects of treatment (single point) or treatment, hour, and their interaction (over time, using repeated measures). Date of calving was a fixed effect; calf sex was included when P &lt; 0.25. Heifers fed CON had greater (P = 0.04) colostrum weight and volume than NR. Although gestational nutrition did not affect (P = 0.72) calf birth weight, calves born to CON heifers had faster (P = 0.02) times to stand and tended to have faster (P = 0.09) times to attempt to stand. Calves from CON heifers had greater (P = 0.05) 20 min vigor scores. Rectal temperatures at 0 h were greater (P = 0.02) in CON calves, but at 24 h were greater (P = 0.04) in NR calves. These data indicate that heifers nutrient restricted during late gestation have reduced colostrum yield and less vigorous calves, which may influence postnatal calf survival.


2021 ◽  
Vol 99 (Supplement_2) ◽  
pp. 25-26
Author(s):  
Sterling H Fahey ◽  
Sarah West ◽  
John M Long ◽  
Carey Satterfield ◽  
Rodolfo C Cardoso

Abstract Gestational nutrient restriction causes epigenetic and phenotypic changes that affect multiple physiological processes in the offspring. Gonadotropes, the cells in the anterior pituitary that secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH), are particularly sensitive to nutritional changes during fetal development. Our objective herein was to investigate the effects of gestational nutrient restriction on LH protein content and number of gonadotropes in the fetal bovine pituitary. We hypothesized that moderate nutrient restriction during mid to late gestation decreases pituitary LH production, which is associated with a reduced number of gonadotropes. Embryos were produced in vitro with X-bearing semen from a single sire then split to generate monozygotic twins. Each identical twin was transferred to a virgin dam yielding four sets of female twins. At gestational d 158, the dams were randomly assigned into two groups, one fed 100% NRC requirements (control) and the other fed 70% of NRC requirements (restricted) during the last trimester of gestation, ensuring each pair of twins had one twin in each group. At gestational d 265, the fetuses (n = 4/group) were euthanized by barbiturate overdose, and the pituitaries were collected. Western blots were performed using an ovine LH-specific antibody (Dr. A.F. Parlow, NIDDK). The total LH protein content in the pituitary tended to be decreased in the restricted fetuses compared to controls (P &lt; 0.10). However, immunohistochemistry analysis of the pituitary did not reveal any significant changes in the total number of LH-positive cells (control = 460±23 cells/0.5 mm2; restricted = 496±45 cells/0.5 mm2, P = 0.58). In conclusion, while maternal nutrient restriction during gestation resulted in a trend of reduced LH content in the fetal pituitary, immunohistological findings suggest that these changes are likely related to the individual potential of each gonadotrope to produce LH, rather than alterations in cell differentiation during fetal development.


Author(s):  
Mark H. Oliver ◽  
Frank H. Bloomfield ◽  
Amita Bansal ◽  
Hui Hui Phua ◽  
Eric B. Thorstensen ◽  
...  

Abstract Maternal periconceptional undernutrition (PCUN) affected fetal pancreatic maturation in late gestation lambs and impaired glucose tolerance in 10-month-old sheep. To examine the importance of the timing of maternal undernutrition around conception, a further cohort was born to PCUN ewes [undernourished for 61 d before conception (PreC), 30 d after conception (PostC), or 61 d before until 30 d after conception (PrePostC)], or normally fed ewes (Control) (n = 15–20/group). We compared glucose tolerance, insulin secretion, and sensitivity at 36 months of age. We also examined protein expression of insulin signalling proteins in muscle from these animals and in muscle from a fetal cohort (132 d of gestation; n = 7–10/group). Adult PostC and PrePostC sheep had higher glucose area under the curve than Controls (P = 0.07 and P = 0.02, respectively), whereas PreC sheep were similar to Controls (P = 0.97). PostC and PrePostC had reduced first-phase insulin secretion compared with Control (P = 0.03 and P = 0.02, respectively). PreC was similar to Control (P = 0.12). Skeletal muscle SLC2A4 protein expression in PostC and PrePostC was increased 19%–58% in fetuses (P = 0.004), but decreased 39%–43% in adult sheep (P = 0.003) compared with Controls. Consistent with this, protein kinase C zeta (PKCζ) protein expression tended to be increased in fetal (P = 0.09) and reduced in adult (P = 0.07) offspring of all PCUN ewes compared with Controls. Maternal PCUN alters several aspects of offspring glucose homeostasis into adulthood. These findings suggest that maternal periconceptional nutrition has a lasting impact on metabolic homeostasis of the offspring.


2012 ◽  
Vol 109 (11) ◽  
pp. 2098-2110 ◽  
Author(s):  
M. O. Nielsen ◽  
A. H. Kongsted ◽  
M. P. Thygesen ◽  
A. B. Strathe ◽  
S. Caddy ◽  
...  

We have developed a sheep model to facilitate studies of the fetal programming effects of mismatched perinatal and postnatal nutrition. During the last trimester of gestation, twenty-one twin-bearing ewes were fed a normal diet fulfilling norms for energy and protein (NORM) or 50 % of a normal diet (LOW). From day 3 postpartum to 6 months (around puberty) of age, one twin lamb was fed a conventional (CONV) diet and the other a high-carbohydrate–high-fat (HCHF) diet, resulting in four groups of offspring: NORM-CONV; NORM-HCHF; LOW-CONV; LOW-HCHF. At 6 months of age, half of the lambs (all males and three females) were slaughtered for further examination and the other half (females only) were transferred to a moderate sheep diet until slaughtered at 24 months of age (adulthood). Maternal undernutrition during late gestation reduced the birth weight of LOW offspring (P< 0·05), and its long-term effects were increased adrenal size in male lambs and adult females (P< 0·05), increased neonatal appetite for fat-(P= 0·004) rather than carbohydrate-rich feeds (P< 0·001) and reduced deposition of subcutaneous fat in both sexes (P< 0·05). Furthermore, LOW-HCHF female lambs had markedly higher visceral:subcutaneous fat ratios compared with the other groups (P< 0·001). Postnatal overfeeding (HCHF) resulted in obesity (>30 % fat in soft tissue) and widespread ectopic lipid deposition. In conclusion, our sheep model revealed strong pre- and postnatal impacts on growth, food preferences and fat deposition patterns. The present findings support a role for subcutaneous adipose tissue in the development of visceral adiposity, which in humans is known to precede the development of the metabolic syndrome in human adults.


2006 ◽  
Vol 46 (7) ◽  
pp. 725 ◽  
Author(s):  
A. W. Bell

Human epidemiological evidence has suggested that metabolic perturbations during fetal life may increase predisposition to cardiovascular disease, type 2 diabetes and obesity in later life. A growing number of controlled experiments on sheep and other large animal species are adding to the already large body of experimental evidence from rat studies in supporting the ‘fetal origins’ hypothesis. Of particular practical relevance are findings that maternal undernutrition in late pregnancy can predispose lambs to glucose intolerance and increased adiposity in early adulthood. This effect may be exacerbated by high energy intakes and limited capacity for muscle growth in undernourished or growth-retarded lambs during early postnatal life. Recent Australian studies have demonstrated the effects of prenatal nutrition on postnatal growth and meat production in beef cattle, and on quantity and quality of wool production in sheep.


2003 ◽  
Vol 284 (5) ◽  
pp. E901-E914 ◽  
Author(s):  
M. Thamotharan ◽  
Robert A. McKnight ◽  
Shanthie Thamotharan ◽  
Doris J. Kao ◽  
Sherin U. Devaskar

We examined the long-term effect of in utero exposure to streptozotocin-induced maternal diabetes on the progeny that postnatally received either ad libitum access to milk by being fed by control mothers (CM/DP) or were subjected to relative nutrient restriction by being fed by diabetic mothers (DM/DP) compared with the control progeny fed by control mothers (CM/CP). There was increased food intake, glucose intolerance, and obesity in the CM/DP group and diminished food intake, glucose tolerance, and postnatal growth restriction in the DM/DP group, persisting in the adult. These changes were associated with aberrations in hormonal and metabolic profiles and alterations in hypothalamic neuropeptide Y concentrations. By use of subfractionation and Western blot analysis techniques, the CM/DP group demonstrated a higher skeletal muscle sarcolemma-associated ( days 1 and 60) and white adipose tissue plasma membrane-associated ( day 60) GLUT4 in the basal state with a lack of insulin-induced translocation. The DM/DP group demonstrated a partial amelioration of this change observed in the CM/DP group. We conclude that the offspring of a diabetic mother with ad libitum postnatal nutrition demonstrates increased food intake and resistance to insulin-induced translocation of GLUT4 in skeletal muscle and white adipose tissue. This in turn leads to glucose intolerance and obesity at a later stage ( day 180). Postnatal nutrient restriction results in reversal of this adult phenotype, thereby explaining the phenotypic heterogeneity that exists in this population.


2007 ◽  
Vol 2007 ◽  
pp. 121-121
Author(s):  
T.M. Boland ◽  
L. Hayes ◽  
J.J. Murphy ◽  
J.J. Callan ◽  
T.F. Crosby

Approximately 75% of ewes are housed in Ireland for some portion of the winter, normally the late gestation period. This coincides with a large increase in dietary requirements, with 80% of lamb birth weight laid down in the final two months of gestation (Robinson, 1990) and also udder development during this period. Traditionally, these nutritional requirements were met by feeding grass silage ad libitum and supplementing with concentrates on a stepped rate with advancing pregnancy. With the introduction of the decoupled single farm payment and an ever-decreasing labour supply, sheep producers are looking for financially attractive, low labour alternatives and a concentrate based diet may be one such alternative. The objectives of this experiment were to compare an all concentrate diet supplemented with different fibre sources with the standard silage based diet supplemented with concentrates on feed intake, ewe performance and lamb growth to weaning.


1996 ◽  
Vol 150 (2) ◽  
pp. 231-242 ◽  
Author(s):  
S M Woodall ◽  
B H Breier ◽  
B M Johnston ◽  
P D Gluckman

Abstract While it is well established that severe maternal undernutrition during pregnancy causes intrauterine growth retardation (IUGR), there has been relatively little study of the endocrine consequences and postnatal development of growth-retarded offspring. We have developed a model in the rat of IUGR by nutritional restriction of the mother throughout gestation and have examined the effects of fetal growth retardation on the endocrine and metabolic status during the perinatal period. Timed matings were performed in Wistar rats and dams were randomly assigned to one of two dietary treatment groups. Food was available ad libitum throughout pregnancy to a control group (ad libitum group) and a restricted group was fed 30% of the ad libitum intake (restricted fed group). After birth, food was available ad libitum in both groups and litter size was adjusted to eight pups per litter. Dams lost a significant amount of body weight throughout gestation due to undernutrition but were able to catch up to the ad libitum group by day 10 postnatally. Litter size was not affected by maternal undernutrition. Maternal plasma IGF-I levels were significantly reduced in the restricted fed group throughout gestation (P<0·001) but were not different postnatally. Maternal plasma IGF-binding proteins (IGFBPs)-1, -2 and -3 were significantly (P<0·05) increased in the restricted fed dams. The mean body weights of fetuses in late gestation from the restricted fed dams were significantly lower (P<0·001) in comparison with fetuses from control dams. Placental weights were also significantly (P<0·01) reduced in the restricted fed compared with control dams. Body weights were significantly lower in the offspring of restricted fed dams than control dams from birth (P<0·01) until 90 days of age (P<0·05). Nose–rump length was reduced in the fetuses of the restricted fed group at day 22 of gestation (P<0·001) until weaning (P<0·05). Plasma IGF-I levels were significantly reduced in the pups of restricted fed dams from day 22 of gestation (P<0·01) until postnatal day 9 (P<0·05) but were not significantly different at the later time-points. Plasma insulin levels were significantly reduced in the pups of restricted fed dams at birth (P<0·05) but not at later time-points. Plasma IGFBP-1 and -2 levels were significantly increased in the offspring from restricted fed dams at day 22 of gestation, at birth and at day 9 postnatally (P<0·05). 125I-Bovine GH specific binding to liver membranes was significantly lower (P<0·05) in offspring from restricted fed dams at 21 days of age but not at 90 days of age. These data demonstrate that nutritional deprivation in the pregnant rat leads to IUGR and postnatal growth failure and to changes in allometric growth patterns and endocrine parameters of the somatotrophic axis postnatally. Journal of Endocrinology (1996) 150, 231–242


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2238-2238
Author(s):  
Sung Park ◽  
Kavitha Gnanasambandan ◽  
Peter P. Sayeski

Abstract Abstract 2238 In early Jak2 murine models, conventional germline knockout of Jak2 tyrosine kinase resulted in embryonic lethality at E12.5 due to severe defects in hematopoiesis. However, what role, if any, that Jak2 plays in late gestational development and post natal life is currently unknown. To achieve some understanding of this, we utilized a conditional knockout approach that allowed for the temporal deletion of Jak2 at various stages of embryonic and postnatal growth. Specifically, Jak2 conditional knockout mice were produced by crossing estrogen receptor inducible Cre mice (RosaCreER) with loxP inserted Jak2 conditional knockout mice (FL/FL). Injection of the bigenic mice with tamoxifen (TM), a synthetic estrogen receptor modulator, accordingly results in a Jak2 null allele. TM was injected into pregnant dams at E12.5 and into postnatal mice at day 4 and day 60. The animals were then euthanized at E16.5 (late gestation), postnatal at day 18 (an active stage of postnatal development) and day 90 (adult stage), respectively. We found that deletion of Jak2 throughout all stages of murine development resulted in marked hypocellular bone marrow, significantly reduced spleen size, an absence of extramedullary hematopoiesis, and profound anemia. Analysis of peripheral blood samples indicated that the Jak2 null mice have significantly decreased hematocrits characterized by increased numbers of abnormal red blood cells that were either immature or lacking hemoglobin. Furthermore, the number of platelets was also significantly reduced in the null mice when compared to aged matched littermate controls. Overall, these results indicate that Jak2 plays a critical and non-redundant role in hematopoiesis throughout all stages of prenatal and postnatal life. Disclosures: No relevant conflicts of interest to declare.


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