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Poor maternal nutrition can negatively affect fetal and placental growth and development. However, the mechanism(s) that contribute to altered placenta growth and function are not well understood. We hypothesized that poor maternal diet would impact signaling through the C-X-C motif chemokine ligand (CXCL) 12-CXCL4 axis and/or placental expression of the insulin-like growth factor (IGF) axis. Using our established sheep model of poor maternal nutrition, we examined the effects of restricted- and over-feeding on ewe placentome gene and protein expression. Specifically, ewes were fed a control (CON; 100%), restricted (RES; 60%), or over (OVER; 140%) diet beginning at day 30.2 ± 0.02 of gestation, and samples were collected at days 45, 90, and 135 of gestation, representing periods of active placentation, peak placental growth, and near term, respectively. Placentomes were separated into cotyledon and caruncle, and samples snap frozen. Protein was determined by western blot and mRNA expression by real-time PCR. Data were analyzed by ANOVA and significance determined at P ≤ 0.05. Ewes fed a RES diet had decreased CXCL12 and vascular endothelial growth factor (VEGF), and increased tumor necrosis factor (TNF)α protein compared with CON ewes in caruncle at day 45 (P ≤0.05). In day 45 cotyledon, CXCR7 protein was increased and mTOR was decreased in RES relative to CON (P ≤0.05). At day 90, CXCR4 and CXCR7 were reduced in RES caruncle compared with CON, whereas VEGF was reduced and mTOR increased in cotyledon of RES ewes relative to CON (P ≤0.05). In OVER caruncle, at day 45 CXCR4 and VEGF were reduced and at day 90 CXCR4, CXCR7, and TNFα were reduced in caruncle compared with CON (P ≤0.05). There was no observed effect of OVER diet on protein abundance in the cotyledon (P > 0.05). Expression of IGF-II mRNA was increased in OVER at day 45 and IGFBP-3 was reduced in RES at day 90 in caruncle relative to CON (P ≤0.05). Maternal diet did not alter placentome diameter or weight (P > 0.05). These findings suggest that restricted- and over-feeding negatively impact protein and mRNA expression of key chemokines and growth factors implicated in proper placenta development and function. [ABSTRACT FROM AUTHOR]

Improper placentation is the root cause to intrauterine growth restriction (IUGR) and fetal mortality in livestock. This study aims to further characterize the importance of the C-X-C motif chemokine receptor 4 (CXCR4) and its ligand CXCL12 on placentation and fetal growth through potential impacts on the insulin-like growth factors (IGF) and their binding proteins (IGFBP1-3). CXCR4 and CXCL12 are implicated in placentation though the exact roles are unclear. The peptides insulin-like growth factors 1 and 2 have impacts on fetal growth, placental development, and trophoblast differentiation and if the IGFs are down regulated, a corresponding decrease in placenta and fetus size has been observed. The roles of the IGFs and their binding proteins in disease states like IUGR are not completely known but studies have demonstrated them to be contributing factors. Using an in-vivo sheep model we surgically inserted osmotic pumps on day 12 (d12) of gestation ipsilateral to the corpus luteum to deliver treatments into the uterus of bred ewes. Pumps delivered either saline (control) or AMD3100, the CXCR4 inhibitor at a 1x, 1.5x, or 3x dose into the uterine lumen over the course of 14 days. Our objective was to determine if disrupting the CXCL12/ CXCR4 axis during implantation alters the expression of IGFs and their binding proteins in the placenta at mid and late gestation. At midgestation (d90) and late gestation (d135) placental and fetal samples were obtained for analysis. Of the targets tested, mRNA expression was significantly decreased by AMD3100 treatment for both IGF-1 (P = 0.05) and IGF-2 (P = 0.02) compared to control primarily in maternal placenta tissues on d135. For fetal tissue samples, d90 mRNA expression for IGF-1 (P = 0.04) IGFBP-2 (P = 0.02) and IGFBP-3 (P = 0.03) increased in the 3x AMD3100 treated group compared to the control while in d135 samples, IGF-1was significantly decreased (P = 0.04) by the 1x treatments compared to control. Our preliminary data show an importance of the CXCL12- CXCR4 signaling on placentation and that impairment of this axis may alter IGFs in multiple tissue types later in gestation. Insights into this chemokine axis will lead to a greater understanding of placental development and its importance to the health of mother and offspring. [ABSTRACT FROM AUTHOR]

Placental dysfunction is a fundamental cause of intrauterine growth restriction, and fetal morbidity and mortality in livestock. Though causes of placental dysfunction are not well characterized, origin of disease transpires during placental development (placentation). The C-X-C motif chemokine ligand 12 (CXCL12) working through its receptor CXCR4 is implicated in placentation but precise roles of this axis are unclear. Using an in vivo sheep model, we demonstrated that suppressing CXCL12-CXCR4 signaling at the fetal-maternal interface reduces placental vascularization. We hypothesized these negative impacts early in gestation would result in compromised placental development and vascularization at midgestation. To test, onday 12 post-breeding, osmotic pumps were surgically installed in 22 ewes and delivered either CXCR4 inhibitor (AMD3100) at 1.5X dose, (n=8) or 3X dose (n=8) or saline (n=6) into the uterine lumen ipsilateral to the corpus luteum for 14 days. On day 90 placental tissues were collected and maternal and fetal placenta components separated and analyzed. The objectives were to determine if suppressing CXCL12-CXCR4 actions at the fetal-maternal interface during implantation results in reduced placental and vascular development at midgestation. Gene expression for angiogenic factors and members of the insulin-like growth factor family were analyzed using Real-time qPCR. Of the targets tested, mRNA expression was significantly altered by AMD3100 treatment for the vascular endothelial growth factor receptors (FLT-1 and KDR) primarily in maternal placenta. Expression of insulinlike growth factors 1 and 2, IGF-binding protein 3, and placental lactogen were significantly altered in fetal placenta with AMD3100 treatment compared to control. Our preliminary data underscore the importance of CXCL12-CXCR4 signaling during placentation and provide strong evidence that altering CXCL12-mediated signaling during early placentation induces enduring placental effects manifesting later in gestation. A greater understanding of CXCL12/CXCR4 functions may reveal methods to improve reproductive success and fetal health. [ABSTRACT FROM AUTHOR]

The objectives of this study were to investigate the effects of fibroblast growth factor 9 (FGF9) on hormone-stimulated porcine granulosa cell proliferation and steroid production and to further elu-cidate the hormonal and developmental control of FGFR2IĽC gene expression in granulosa cells. Porcine ovaries were collected from a local slaughterhouse and granulosa cells were collected from small to medium ( 1 to 5 mm) follicles for 5 in vitro studies that were con-ducted. Cells were cultured for 48 h in 5% fetal calf serum plus 5% porcine serum and then treated with vari-ous combinations of FSH, IGF-I, FGF9, Sonic hedge-hog (SHH), Cortisol, PGE2, and/or wingless-type mouse mammary tumor virus integration site family member 5A (WNT5A) in serum-free medium for an additional 24 or 48 h. Medium was collected for analysis of ste-roid concentration via RIA, or RNA was collected for gene expression analysis of FGFRllllc via quantitative reverse transcription PCR. Fibroblast growth factor 9 stimulated (P < 0.05) IGF-I-induced estradiol produc-tion in the presence of FSH and testosterone. However, FGF9 had inconsistent effects on progesterone produc-tion, stimulating progesterone production in the pres- ence of FSH and testosterone but inhibiting proges-terone production in the presence of IGF-I, FSH, and testosterone. Cell numbers were increased (P < 0.05) by FGF9 in the presence of IGF-I and FSH but not in the presence of FSH and absence of IGF-I. For FGFRlUlc mRNA studies, granulosa cells were treated with FSH, IGF-I, FGF9, SHH, Cortisol, PGE2, or WNT5A. Folli-cle-stimulating hormone alone had no effect (P >0.10) whereas IGF-I increased (P < 0.05) FGFR2IIIc mRNA abundance. Cortisol, PGE2, SHH, and WNT5A had no effect (P > 0.10) on FGFR2IIIc gene expression whereas FGF9 in the presence of FSH and IGF-I inhibited (P < 0.05) FGFR2IIIc gene expression. In an in vivo study, granulosa cells from large (7 to 14 mm) follicles had greater (P < 0.05) abundance of FGFR2IIIc mRNA than small ( 1 to 3 mm) or medium (4 to 6 mm) follicles. In conclusion, IGF-I-induced FGFR2IĽC mRNA may be a mechanism for increased responses to FGF9 in FSH plus IGF-I-treated granulosa cells. Fibroblast growth factor 9 and IGF-I may work together as amplifiers of follicular growth and granulosa cell differentiation by stimulat-ing estradiol production and concomitantly stimulating granulosa cell growth in pigs. [ABSTRACT FROM AUTHOR]

Cattle genetically selected for twin ovulations and births (Twinner) exhibit increased ovarian follicular development, increased ovulation rate, and greater blood and follicular fluid IGF-1 concentrations compared with contemporary cattle not selected for twins (Control). Experimental objectives were to 1) assess relationships among aromatase (CYP19A1), IGF-1 (IGFl), IGF-2 receptor (IGF2R), and FSH receptor (FSHR) mRNA expression in small (≤5 mm) antral follicles and 2) determine their association with increased numbers of developing follicles in ovaries of Twinner females. Ovaries were collected from mature, cyclic (d 3 to 6) Twinner (n = 11), and Control (n = 12) cows at slaughter and pieces of cortical tissue were fixed and embedded in paraffin. Expression of mRNA was evaluated by in situ hybridization using 35S-UTP-labeled antisense and sense probes for CYP19A1, FSHR, IGFl, and IGF2R mRNA. Silver grain density was quantified within the granulosa and theca cells of individual follicles (2 to 7 follicles/cow) by Bioquant image analysis. Follicles of Twinners tended to be smaller in diameter than Controls (1.9 ± 0.1 vs. 2.3 ± 0.1 mm; P = 0.08), but thickness of granulosa layer did not differ (P > 0.1) by genotype. Relative abundance of CYP19A1 (P < 0.01) and FSHR (P < 0.05) mRNA was greater in granulosa cells of Twinners vs. Controls, respectively, whereas IGF2R mRNA expression was less in both granulosa (P < 0.01) and theca (P < 0.05) cells in follicles of Twinners vs. Controls, respectively. Abundance of CYP19A1 mRNA in granulosa cells was correlated negatively with IGF2R mRNA expression in both granulosa (r = -0.33; P < 0.01) and theca (r = -0.21 ; P = 0.05) cells. Expression of IGFl mRNA was primarily in granulosa cells, including cumulus cells, and its expression did not differ between Twinners vs. Controls (P > 0.10). Detected increases in CYP19A1 and FSHR, but not IGFl, mRNA expression along with decreases in IGF2R mRNA expression in individual follicles of Twinners support the hypothesis that increased follicular development and steroidogenesis in Twinner females result from increased extra-ovarian IGF-1 production. Furthermore, a reduction in follicular IGF2R mRNA expression accompanied by a reduction in receptor numbers would increase availability of free IGF-2 and its stimulation of follicular development in Twinners. [ABSTRACT FROM AUTHOR]

Prolactin, glucocorticoids, and insulin are commonly used to induce milk protein synthesis in bovine mammary cell cultures. In addition, administration of GH increases milk yield in dairy cows, likely via the mammalian target of rapamycin (mTOR) pathway and IGF-I synthesis. As such, the hypothesis of this study was that mRNA abundance of hormone receptors, mammalian target of mTOR pathway-related kinases, IGF-I, and milk protein-encoding genes increases in the porcine mammary gland in response to greater lactation demand. Selected genes included those encoding for receptors of GH (GHR), insulin (INSR), glucocorticoid (NRSC1), prolactin (PRLR), IGF-I (IGF-I), mTOR (FRAP1), and p7056 kinases (RPS6KB1), and the milk proteins α-lactalbumin (LALBA) and 13-casein (CSN2). Mammary tissue was biopsied from 4 sows on d 110 of gestation (prepartum), d 5 and 17 of lactation, and d 5 after weaning (postweaning), and gene expression was quantified by reverse-transcription quantitative PCR. Compared with prepartum, d 5 of lactation increased (P < 0.001) NR3C1, tended to increase (P = 0.06) GHR, and decreased (P < 0.001) PRLR mRNA abundance. Compared with d 5 of lactation, d 17 of lactation increased PRLR (P < 0.001) and decreased GHR (P < 0.01). Expression of INR and FRAP1 did not differ when comparing either prepartum or d 17 of lactation with d 5 of lactation. Compared with d 17 of lactation, postweaning decreased (P < 0.001) PRLR, did not affect INSR, and increased both IGF-I and CHR (P < 0.05) mRNA abundance. From prepartum to d 17 of lactation, NRSC1 mRNA abundance was positively correlated with CSN2 (r = 0.85; P < 0.001) and LALBA mRNA abundance (r = 0.79; P = 0.002), whereas mRNA abundance of CHR tended to be positively correlated with that of IGF-I (r = 0.46; P = 0.06). In conclusion, expression of the genes NR3C1, PRLR, GHR, and IGF-I changed in the porcine mammary gland during the prepartum to postweaning periods, but only NR3C1 mRNA abundance was positively correlated with expression of CSN2 and LALBA. [ABSTRACT FROM AUTHOR]

In an effort to determine whether tropical adaptation influences circulating concentrations of the growth-related hormone IGF-I, 3-breed diallel matings were conducted using temperate Bos taurus (Angus), tropical Bos indicus (Brahman), and tropical Bos taurus (Romosinuano). Purebred Angus, Braham, and Romosinuano and crossbred Angus-Braham, Angus-Romosinuano, and Braham-Romosinuano heifers and steers were evaluated in 2 separate calf crops from 2003 and 2004. Blood samples were obtained from 10 heifers of each breed group (n = 90) for each year at weaning and on d 0 and 84 of postweaning trials. Samples were also taken from 10 steers of each breed group (n = 90) at weaning and on d 0 and 60 of individual finishing phase feeding trials for each year. Concentrations of IGF-I were determined by RIA. Analyses included effects of sire breed, dam breed, year of record, the age of the dam of the calf in years, and interactions. Age of calf in days was investigated as a linear and quadratic covariate. Separate analyses were conducted for steers and heifers. The direct effect of Angus was to reduce (P < 0.03) heifer concentrations of IGF-I at d 84 and in the repeated measures analysis. In the repeated measures analysis, the direct effect of Romosinuano was to increase concentrations of IGF-I (P = 0.01). Relative to the temperate Bos taurus breed, plasma concentrations of IGF-I were numerically greater in male and female tropically adapted breed groups. [ABSTRACT FROM AUTHOR]

Seventy-four Angus and Angus × Hereford heifers were used in 2 successive years (yr 1, n = 43; yr 2, n = 31) to determine if luteal function of heifers during acute submaintenance feeding is related to variation in utilization of feed as determined by residual feed intake (RFI). Residual feed intake was determined for heifers beginning at 12.3 ± 0.1 mo of age in yr 1 and at 9.1 ± 0.1 mo of age in yr 2. Heifers were assigned to dry-lot pens (n = 6 to 9 heifers/pen) with electronic gates to measure individual feed intake of a total mixed ration for 70 and 72 d in yr 1 and 2, respectively. Residual feed intake was calculated as the difference between actual DMI and expected DMI from linear regression of DMI on mid-test BW0.75 and ADG. At 14.4 ± 0.1 mo of age, all heifers were provided a restricted amount of feed to supply 40% of their maintenance energy requirements for 21 d. Estrous cycles of heifers were synchronized with PGF2α on d −10, 0, and 11 relative to start of restriction. Concentrations of progesterone in plasma on d 14 to 21 of restriction were used to determine if heifers ovulated. Overall ADG and ADFI were 0.83 ± 0.02 and 7.37 ± 0.67 kg/d, respectively, for yr 1; and 0.50 ± 0.02 and 5.66 ± 0.09 kg/d, respectively, for yr 2. There was no correlation between RFI and BW, ADG, ADFI, or ultrasound measure of backfat, nor was RFI related to concentrations of IGF-I in plasma. All heifers lost BW and had reduced backfat (P < 0.001) at the end of restricted feeding. All heifers had reproductive cycles before dietary restriction started. During acute nutritional restriction, 4 heifers became anovulatory. Sixteen heifers had concentrations of progesterone in plasma during restricted feeding that were atypical of normal luteal function. There was no relationship between luteal function during nutrient restriction and RFI of heifers. Circulating IGF-1 was greater at weaning and after restricted feeding in heifers with a smaller RFI (>0.5 SD below the mean) than heifers with a greater RFI (>0.5 SD above the mean). It is concluded that RFI is not related to luteal function during acute submaintenance feeding, but that short-term restriction of nutrient intake can alter luteal function that may compromise fertility, even in heifers that exhibit estrus and ovulate. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the effects of mutations in 2 genes [IGF2 and cathepsin D (CTSD)J that map on the telomeric end of the p arm of SSC2. In this region, an imprinted QTL affecting muscle mass and fat deposition was reported, and the IGF2 intron3-g.3072G>A substitution was identified as the causative mutation. In the same chromosome region, we assigned, by linkage mapping, the CTSD gene, a lysosornal proteinase, for which we previously identified an SNP in the 3'-untranslated region (AM933484, g.70G>A). We have already shown strong effects of this CTSD mutation on several production traits in Italian Large White pigs, suggesting a possible independent role of this marker in fatness and meat deposition in pigs. To evaluate this hypothesis, after having refined the map position of the CTSD gene by radiation hybrid mapping, we analyzed the IGF2 and the CTSD polymorphisms in 270 Italian Large White and 311 Italian Duroc pigs, for which EBV and random residuals from fixed models were calculated for several traits. Different association analyses were carried out to distinguish the effects of the 2 close markers. In the Italian Large White pigs, the results for ICF2 were highly significant for all traits when using either EBV or random residuals (e.g., using EBV: lean cuts, P = 2.2 × 10-18; ADG, P = 2.6 × 10-16; backfat thickness, P = 2.2 ×-9 feed:gain ratio, P = 2.3 × 10-9 ham weight, P = 1.5 × 10-6). No effect was observed for meat quality traits. The IGF2 intron3-g.3072C>A mutation did not show any association in the Italian Duroc pigs, probably because of the small variability at this polymorphic site for this breed. However, a significant association was evident for the CTSD marker (P < 0.001) with EBV of all carcass and production traits in Italian Duroc pigs (lean content, ADO, backfat thickness, feed:gain ratio) after excluding possible confounding effects of the IGF2 mutation. The effects of the CTSD g.70G>A mutation were also confirmed in a subset of Italian Large White animals carrying the homozygous genotype ICF2 intron3-g.307200, and by haplotype analysis between the markers of the 2 considered genes in the complete data set. Overall, these results indicate that the IGF2 intron3-g.3072G>A mutation is not the only polymorphism affecting fatness and muscle deposition on SSC2p. Therefore, the CTSD g.700>A polymorphism could be used to increase selection efficiency in marker-assisted selection programs that already use the IGF2 mutation. However, for practical applications, because the CTSD gene should not be imprinted (we obtained this information from expression analysis in adult skeletal muscle), the different modes of inheritance of the 2 genes have to be considered. [ABSTRACT FROM AUTHOR]

Data from a selection experiment for residual feed intake (RFI) were used to estimate genetic correlations between measures of efficiency and performance traits with juvenile ICF–I, and to demonstrate direct and correlated responses to selection. The heritability of IGF–I was 0.28 ± 0.06 and genetic correlations of IGF–I with feed intake (0.26 ± 0.17), backfat (0.52 ± 0.11), and feed conversion ratio (0.78 ± 0.14) were moderate to large. The estimated and realized genetic correlations between RFI and IGF–I were 0.63 ± 0.15 and 0.84. In contrast, genetic correlations between IGFI and lifetime or test period growth did not differ (P > 0.05) significantly from zero (0.06 ± 0.14 and –0.19 ± 0.14). Selection for decreased RFI produced a direct response in RFI, as expected, and was accompanied by downward correlated responses in ADFI, juvenile IGFI, backfat, and growth traits, listed in order of decreasing relative magnitude, and an increased loin muscle area. The correlated response in IGF–I to selection on RFI demonstrates that this physiological measure is genetically associated with efficiency, and is thus useful as an early information source to estimate genetic merit for efficiency before performance testing. Decreased juvenile IGF–I is associated with leaner, more efficient animals. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-I in conjunction with gonadotropins are important stimulators of mitosis and ovarian steroid production by granulosa and thecal cells, which are required for normal oocyte development and hormonal feedback signaling to the hypothalamus and pituitary. However, a comprehensive evaluation of the changes in gene expression induced by IGF-I has not been conducted. Our objective was to characterize granulosa cell gene expression in response to IGF-I treatment. Porcine granulosa cells were pooled in 4 biological replicates and treated with FSH (baseline) or FSH+IGF-I for 24 h in vitro. The RNA was collectccl and hybridized to 8 Affymetrix Porcine GeneChips (Affymetrix, Santa Clara, CA) in a paired design. Differentially regulated gene sequence element sets (P < 0.01) were used as queries in the UniGene database searching for annotated genes. Abundance of messenger RNA (mRNA) for genes differentially expressed in the microarray analysis was determined through multiplex assays of one-step real-time reverse transcription-PCR and further analyzed under a statistical model including the fixed effect of treatment. A total of 388 gene sequence element sets were differentially expressed, and 42 matched annotated genes in the UniGene database. Of the 3 upregulatecl target genes selected for further quantitative reverse transcription-PCR. analysis, only FGF receptor 2 III c (FGFR2IIIc) mRNA abundance was significantly increased by IGF-I. Of the 3 dlownregulated target genes selected for further analysis, only thrornbospondin-1 (THBS1) mRNA abuiiclancc was significantly decreased by IGF-I. Further study revealed that neither FSH nor estracliol affected the IGF-I-induced suppression of THBS1 mRNA abundance. These results provide the first comprehensive assessment of IGF-I-inducecl gene expression in granulosa cells and will contribute to a better understanding of the molecular mechanisms of IGF-I regulation of follicular development. Involvement of FGFR2IIIc and THBS1 in mediating IGF-I-induced granulosa cell steroidlogenesis and proliferation during follicular development is novel, but their specific roles will require further elucidation. [ABSTRACT FROM AUTHOR]

We previously showed that a combined trenbolone acetate (TBA)/estradiol-17β (E2) implant significantly increases IGF-I mRNA levels in the LM of feedlot steers by 28 d after implantation. Here we compare the effects of E2 (25.7 mg), TBA (120 mg), and combined TBA (120 mg)/E2 (24 mg) implants on IGF-I, ICF-I receptor (IGFR-1), estrogen receptor (ER)-α and androgen receptor (AR) mRNA levels in the LM of steers. Twenty yearling crossbred steers with an average initial BW of 421.1 ± 3.6 kg were stratified by BW and randomly assigned to 1 of 4 treatments: 1) nonimplanted, control; 2) implanted with TBA and E2; 3) implanted with E2; or 4) implanted with TBA. Steers were weighed weekly starting on d 0, and muscle biopsy samples were taken from each steer on d 0 (before implantation), 7, 14, and 28. Ribonucleic acid was prepared from each sample and real-time reverse transcription-PCR was used to determine the levels of IGF-I, IGFR-1, ER-α, and AR mRNA. Body weight of implanted steers, adjusted by using d-0 BW as a covariant, tended (P = 0.09) to be greater than that of control steers. On d 7 and 28, IGF-I mRNA levels were greater (58 and 78%, respectively; P < 0.009) in E2-implanted animals than in control steers. Similarly, on d 28 the LM IGF-I mRNA level was 65% greater (P = 0.017) in TBA/E2-implanted steers than in control animals. In contrast, the TBA implant did not increase (P = 0.99) LM IGF-I mRNA levels after 28 d of implantation. Muscle IGFR-1, AR, and ER-α mRNA levels were not different (P > 0.47) in any of the treated groups compared with the control group. These data suggest that E2 is responsible for the increased muscle ICF-I mRNA level observed in steers implanted with a combined TBA/E2 implant. [ABSTRACT FROM AUTHOR]

To determine the effects of maternal nutrient restriction and re-alimentation on fetal liver and muscle development, 48 pregnant ewes with singletons, were fed a control diet [100% National Research Council (NRC) requirements (CON)] starting at the beginning of gestation. On day 50 of gestation, ewes (n = 7) were euthanized and fetal liver and skeletal muscle samples were collected. The remaining animals were fed either CON or 60% NRC requirements (RES), a subset were euthanized at day 90 of gestation (n = 7/treatment), and fetal samples obtained. Remaining ewes were maintained on the current diet (CON-CON, n = 6; RES-RES, n = 7) or switched to alternative diet (CON-RES, RES-CON; n = 7/treatment). On day 130 of gestation, remaining ewes were euthanized, and fetal samples collected. Fetal liver was analyzed for general tissue morphology, and fetal skeletal muscles were analyzed for lipid accumulation. mRNA expression of growth and metabolic factors were quantified in liver and muscle tissues. Hepatocellular vacuolation was increased in RES-CON and RES-RES compared with CON-CON and CONRES (P < 0.01). In semitendinosus and triceps brachii, intramyocellular lipid content increased 19% and 15%, respectively, in RES-CON and RES-RES compared with CON-CON and CON-RES (P£0.02) and in longissimus dorsi, lipid content was decreased 7% in CON-RES and RES-RES compared with CON-CON and RES-CON (P=0.01). In liver, insulin-like growth factor binding protein-1, glycogen synthase 2, and pyruvate dehydrogenase kinase 1 expression increased 1.92-fold, 1.45-fold, and 1.47-fold, respectively (P£0.03) in CON-RES and RES-RES compared with RES-CON and CON-CON. In LD, IGF1-R expression increased 3.19-fold in CON-RES and RES-RES compared with RES-CON and CON-CON (P = 0.05). These results demonstrate that maternal nutrient restriction followed by re-alimentation restores liver and muscle gene expression of growth and metabolic factors while negatively impacting liver composition and muscle lipid content potentially leading to altered tissue function and metabolism later in life. Supported by USDA-AFRI grants 2016-67016-24884 and 2017-67016-26568. [ABSTRACT FROM AUTHOR]

The genetic variation of plasma IGF-I in crossbred ewe lambs postweaning was evaluated together with its potential use as a physiological marker for selection in meat sheep. Genetic variation for IGF-I was analyzed among 1,246 young crossbred ewes that were the progeny of 30 sires from various maternal breeds and Merino dams. The estimate of heritability of IGF-I was 0.28 ± 0.10, with sire breed not being sig- nificant. Genetic correlations were estimated between IGF-I and performance traits of the ewes, including feed intake, growth, body composition, wool, and reproduction over 3 matings. Although the genetic correlations had high standard errors because of the limited size of the data set, the correlation between IGF-I and grazing feed intake of the mature ewes at maintenance was positive (0.32 ± 0.31). The genetic correlations of IGF-I with other traits ranged from positive and low to moderate for growth (0.05 to 0.36), positive for ultrasound eye muscle depth (0.15), and negative for ultrasound fat depth (-0.12) in the mature ewes, and close to zero for the wool traits. The genetic correlation between IGF-I and the average number of lambs born per ewe mated was negative (-0.18), whereas that for the average number of lambs weaned per ewe mated was positive (0.10). The parameters indicated that genetic variation exists for IGF-I in sheep, and selection for low IGF-I in young ewes may result in some reduction in feed intake and improvement in maintenance efficiency of mature ewes under grazing, with little impact on other production traits. However, the genetic cor- relations had high standard errors, and more precise estimates of these parameters are required for genetic evaluation and to predict with confidence the outcome of breeding programs. [ABSTRACT FROM AUTHOR]

The article presents abstracts on animal breeding and genetics topics which include heritability estimates for fatty acid quantity in Angus beef, relationship of juvenile insulin-like growth factor-I with performance traits in lines selected for residual feed intake, and the incidence of porcine circovirus associated disease in a composite swine population.

The article presents abstracts related to reproductive physiology of livestock and poultry. They include "Effect of progestin treatment on formation of persistent follicles in beef heifers," "Effect of insulin-like growth factor-1 during culture on blastocyst mRNA abundance and survival in utero to day 14 of bovine embryos produced in vitro," and "Progesterone postpartum determination and reproductive performance of crossbred cows."

The transition of pregnancy to lactation, with the concomitant negative energy balance during early lactation, requires substantial adaptive performance of the cow. Apart from clinical disease problems, the identification of cows with suboptimal adaptation is relevant to be able to adequately treat these animals or modify the ration. Effective approaches are necessary to provide maximal information at the earliest time possible. We therefore aimed to identify a measurement that, when applied at a defined point in time relative to calving, was relevant as much as possible to other information on metabolic and health status during early lactation. Blood samples were collected weekly from 4 wk antepartum to 12 wk postpartum from 38 high-yielding Holstein-Friesian cows. Non-esterified fatty acids, beta-hydroxybutyrate, IGF-I, and leptin were measured in serum, and BCS was recorded. Health status was characterized using the concentrations of haptoglobin, the number of leukocytes and neutrophils, as well as the activity of glutamate dehydrogenase (GLDH) in blood to evaluate liver status. Using the factors related to fat mobilization, the animals were classified according to their values recorded at one defined point in time or time interval as being above or below certain thresholds. For each criterion, the groups classified were compared with regard to the time-course yielded from all recordings. From 7 criteria of classification, the most closely related to the variables of fat mobilization was obtained when using NEFA and IGF-I (thresholds of 0.5 mM and 39 ng/mL in wk 1 postpartum, respectively). Both items were then combined into to the criterion NEFA + IGF-I. Applying these criteria, the relations to indices of health and liver status were detectable on the basis of NEFA- and NEFA + IGF-I-classes, which yielded differences in both GLDH and leukocyte numbers. Animals with NEFA > 0.5 mM showed increased GLDH activity but decreased leukocyte numbers. The time and effort required for measuring the IGF-I-concentration in addition to NEFA is not justified for evaluating the metabolic status. Nonesterified fatty acid values ≥0.5 mM during the first week of lactation were considered as the most suitable criterion for identifying limited adaptive performance. [ABSTRACT FROM AUTHOR]

A total of 59 gilts (BW = 137.7 kg) from 3 breeding groups were used to assess the effects of feeding ʟ-carnitine during gestation on gilt growth characteristics, blood metabolites, and uterine and chorioallantoic expression of IGF axis components at d 40, 55, and 70 of gestation. Experimental treatments were arranged in a 2 × 3 factorial, with main effects of added ʟ-carnitine (0 or 50 ppm) and day after initial breeding (d 40, 55, or 70 of gestation). All gilts received a constant feed allowance of 1.75 kg/d and a top-dress containing 0 or 50 ppm of ʟ-carnitine beginning on the first day of breeding through the assigned day of gestation. No dietary treatment differences were observed for gilt BW, backfat, or estimated protein or fat mass at any day of gestation. No differences were observed in circulating total and free carnitine at breeding, but concentrations increased (P < 0.01) as day of gestation increased for gilts fed diets containing ʟ-carnitine compared with those fed the control diet. Maternal IGF-I concentration decreased (P < 0.01) from d 0 to 70 for all gilts, with no differences between treatments. Insulin-like growth factor binding protein-3 mRNA (P = 0.05) and IGFBP-5 mRNA (P = 0.01) increased in the endometrium of gilts supplemented with ʟ-carnitine. These data demonstrate that a-carnitine supplementation and day of gestation alter the expression of the IGF axis by changing the expression of IGFBP at the fetal-maternal interface in swine. These changes in the IGF axis at the fetal maternal interface may aid in determining the reasons for the effects of a-carnitine on reproductive traits. [ABSTRACT FROM AUTHOR]

The aim of this study was to characterize concentrations of leptin, IGF-I, and thyroid stimulating hormone (TSH) in the blood serum of mares pre- and postpartum, in the milk serum of mares postpartum, and in the blood serum of their foals. Nine pregnant Quarter Horse mares and their offspring were used in this study. Once weekly between 1000 and 1200 h for 2 wk before their predicted parturition date, mares were weighed, assigned a BCS, and blood was sampled via jugular venipuncture. Within 2 h of parturition and before the foals nursed (d 0), blood samples were obtained from the mares and foals, and a milk sample was collected from the mares. Blood from the foals and blood and milk from the mares were collected again at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 12, 19, 26, 33, and 61 d postpartum. Mares and foals also were weighed and assigned a BCS on d 0, 5, 12, 19, 26, 33, and 61. Additionally, on d 5, 33, and 61, ultrasound images of fat depth and area of the LM immediately cranial to and parallel with the last rib on the left side of the foals were measured to characterize changes in fat depth and LM area over time. There were no changes in mare blood concentrations TSH (P = 0.15), nor were there any changes in foal blood concentrations of leptin (P = 0.54) or TSH (P = 0.10) during the trial period. Mare blood concentrations of IGF-I tended to change over time (P = 0.07), whereas leptin changed over time (P < 0.001), initially decreasing and then remaining relatively stable after d 5. Foal blood concentrations of IGF-I increased initially, peaked at d 19, and stabilized thereafter (P < 0.001). Milk concentrations of leptin and TSH were greatest on d 0 and decreased over time (P < 0.007), reaching nadir concentrations at d 61. Milk concentrations of IGF-I also changed over time (P = 0.02), being greatest on d 0 and undetectable by d 12. There was no difference in BCS (P = 0.94) in mares over time, but there was a difference between pre- and postpartum BW (P < 0.001) due to foaling. However, no differences were detected in pre- (P = 0.70) or post- partum BW (P = 0.76) of mares over time. Mean ultrasonic fat depth and LM area increased (P < 0.04) as the foals aged, as did BCS and BW (P < 0.001). Recognizing changes in metabolic hormones surrounding the time of parturition in the mare and foal provides a basis for further determination of the role, if any, these hormones play in the milk, as well as in the neonate. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-1 could be a useful marker in the horse for diagnostic, selection, or forensic purposes, provided its physiological regulation is well understood. The objective of this study was to investigate factors, such as acute exercise, fitness training, time of day, sex, and age, that may influence serum IGF-1 in normal, healthy horses. Throughout a 9-wk training program, 6 geldings maintained a mean (±SEM) IGF-1 concentration of 302±29 ng/mL. Moderate or high intensity exercise had no effect on IGF-1 concentrations, when pre-and postexercise values were compared. Over a 24-h period, there was some variation in IGF-1 concentrations but no clear diurnal rhythm, Concentrations of IGF-1 were measured in a large population of thoroughbred horses (1,880) on 3 continents, The population deviated slightly from a normal distribution (P < 0.001) because of large IGF-1 concentrations in 10 horses. The global mean IGF-1 concentration was 310 ± 2.2 ng/mL, with a greater mean value (P < 0.001) in gonad-intact males (336 ± 5.6 ng/mL) than in females (303 ± 3.2 ng/mL) or geldings (302 ± 3.2 ng/mL). However, the greatest IGF-1 concentrations observed for all stallions, mares, and geldings were 627, 676, and 709 ng/mL, respectively. In mares and geldings, IGF-1 concentrations showed a gradual decrease with advancing age (P < 0.001), but the effect was much less marked in stallions. This study confirms that IGF-1 concentrations are stable, compared with GH concentrations, in the horse and that a meaningful measure of IGF-1 status can be obtained from a daily serum sample. [ABSTRACT FROM AUTHOR]

Twenty harrows were used to determine if partial replacement of protein-bound AA with crystalline AA (CAA) reduces AA use for muscle tissue and whole-body growth. Barrows (44.2 ± 1.3 kg of BW) were assigned to 4 diets in a randomized complete block design. Diets consisted of 16.1% CP with no CAA, and 12.8, 10.1, and 7.8% CP containing CAA. As the CP concentration decreased, CAA were gradually increased to meet requirements on a true ileal digestibility basis. Barrows were weighed on d 0 and 13. Blood samples were collected before the morning feeding on d 0, 6, and 12 (prefeeding), and 2 h after the morning feeding on d 13 (postfeeding). Pigs were euthanized on d 13, and liver and right LM were removed and weighed. The reduction in the dietary CP concentration linearly decreased (P < 0.01) ADG, G:F, LM weight, and the CP content of LM. Reducing the CP concentration de- creased pre- and postfeeding plasma concentrations of IGF-I (linear, P < 0.01) and insulin (linear, P < 0.10). The reduction in the dietary CP concentration increased prefeeding plasma concentrations of Ala, Gln, Gly, and total AA but decreased Arg, Asn, His, Ile, Phe, Trp, and Tyr (linear, P < 0.05). Plasma concentration of total indispensable AA decreased initially and increased

Twenty harrows were used to determine if partial replacement of protein-bound AA with crystalline AA (CAA) reduces AA use for muscle tissue and whole-body growth. Barrows (44.2 ± 1.3 kg of BW) were assigned to 4 diets in a randomized complete block design. Diets consisted of 16.1% CP with no CAA, and 12.8, 10.1, and 7.8% CP containing CAA. As the CP concentration decreased, CAA were gradually increased to meet requirements on a true ileal digestibility basis. Barrows were weighed on d 0 and 13. Blood samples were collected before the morning feeding on d 0, 6, and 12 (prefeeding), and 2 h after the morning feeding on d 13 (postfeeding). Pigs were euthanized on d 13, and liver and right LM were removed and weighed. The reduction in the dietary CP concentration linearly decreased (P < 0.01) ADG, G:F, LM weight, and the CP content of LM. Reducing the CP concentration de- creased pre- and postfeeding plasma concentrations of IGF-I (linear, P < 0.01) and insulin (linear, P < 0.10). The reduction in the dietary CP concentration increased prefeeding plasma concentrations of Ala, Gln, Gly, and total AA but decreased Arg, Asn, His, Ile, Phe, Trp, and Tyr (linear, P < 0.05). Plasma concentration of total indispensable AA decreased initially and increased

To assess the efficacy of growth-promoting agents among seasons, triiodothyronine (T3), thyroxine (T4), plasma urea nitrogen (PUN), IGF-I, and tympanic temperature (TT) were measured in summer and winter studies. Heifers (n = 9/pen) were allotted to 12 pens in both December and June. Pens were assigned to 1 of 6 growth promotant treatments: control (no growth promotant), estrogenic implant (E), trenbolone acetate implant (TBA), E + TBA (ET), melengestrol acetate (MGA), and ET + MGA (ETM). Blood samples were collected from 4 heifers per pen per study on d 0, 28, 56, and 84 via jugular puncture. Near the midpoint of both studies, TT were obtained from the heifers. There was a season by sample day interaction for all blood metabolites (P < 0.05). During the winter, IGF-I levels peaked on d 28, whereas T3, T4, and PUN peaked on d 56. In the summer, IGF-I levels increased from d 0 to 28 and remained elevated throughout the study. Season by growth promotant interactions (P < 0.05) indicated that in the winter ET increased T3, whereas TBA alone decreased both T3 and T4, compared with control, or ET, and ETM treatment groups. Across seasons, treatments ET and ETM increased (P < 0.05) IGF- I and decreased (P < 0.05) PUN. However, E, TBA, and MGA alone had no effect on IGF-I or PUN concentrations. The maximum TT was greater (P < 0.01) in the summer than in the winter, whereas the minimum TT was lower (P < 0.01) in the summer. Mean TT did not differ among growth-promoting treatments. However, in the summer and over both seasons, the maximum TT was lower (P < 0.05) in E-, MGA-, and ETM-treated heifers. Although limited growth promotant by season interactions existed, changes in blood metabolite levels resulting from the use of growth promotants do not appear to influence seasonal changes in body temperature as measured by TT. [ABSTRACT FROM AUTHOR]

The objectives of this study were to use transgenic sows that overexpress IGF-I in milk to investigate the effect of a short-term fast on piglet intestinal morphology and disaccharidase activity and to determine how milk-borne IGF-I influences the response to fasting. After farrowing, litters were normalized to 10 piglets. On d 6, piglets (n = 30) suckling IGF-I transgenic (TG) sows and piglets (n = 30) suckling non-transgenic sows (control) were assigned randomly to three treatments: fed piglets (0 h), which remained with the sow until euthanized on d 7, or fasted piglets, which were removed from the sow at either 6 or 12 h before euthanasia on d 7. Serum IGF-I and IGFBP, intestinal weight and length, jejunal protein and DNA content, disaccharidase activity, and villus morphology were measured. Fasting for 12 h resulted in a negative weight change between d 6 and 7 (quadratic response to fasting; P < 0.00 1). Piglets suckling TG sows tended to have greater intestinal length (P = 0.068), but no effect of IGF-I overexpression was noted for intestinal weight. Fasting, however, resulted in linear (P < 0.001) and quadratic (P = 0.002) decreases in intestinal weight. Serum IGF-I did not differ between control and TG sows, but decreased linearly (P = 0.003) with fasting. Serum IGFBP-4 decreased (linear and quadratic; P ⩽ 0.02) with fasting, whereas IGFBP-1 increased quadratically (P < 0.00 1) with fasting. Jejunal villus height, width, and crypt depth were all increased with fasting (linear and quadratic; P < 0.04). Disaccharidase activity was not affected by fed state; however, piglets suckling TG sows had greater jejunal lactase-phlorhizin hydrolase (P < 0.01) and sucrase-isomaltase (P = 0.02) activities than control piglets. In summary, intestinal weight, villus morphology, serum IGF-I, serum IGFBP- 1 and -4, and piglet BW change were altered (P ⩽ 0.02) in response to fasting. Thus, the duration of food deprivation before euthanization should be considered when designing experiments to assess intestinal development or the IGF axis, as the magnitude of differences between the fed and fasted state may exceed those expected as a result of experimental treatment. [ABSTRACT FROM AUTHOR]

The article presents abstracts from papers related to ruminant animal production that were published in the February 2005 issue of the "Journal of Animal Science." The paper "Relationship of Prepartum Concentrations of Insulin-Like Growth Factor-1 (IGF-1) in Cows With Birth Weight, Concentrations of IGF-1, and Weaning Weights of Calves," by R. Flores, M.L. Looper, K.P. Coffey, W.K. Coblentz and C.F. Rosenkrans, Jr., determined relationships between maternal concentrations of IGF-1 during gestation in grazing beef cows and subsequent calf birth weight, concentrations of calf IG F-1 at birth, weaning weights of calves, and resumption of luteal activity in cows. The paper "Effects of Cool Season Annuals With Legumes on Wintering Beef Cows," by J.D. Shockey, W.A. Whitworth, T.G. Montgomery and S.A. Gunter, evaluated the effect of adding legumes to wheat and ryegrass grazing systems as a supplement to gestating beef cows. The paper "Effects of Time of Castration on Growth, Feed-Lot Performance, and Carcass Characteristics of Angus and Charolais-Sired Calves," by M.L. Looper, J.M. Burke, L.J. McBeth, C.R. krehbiel, R. Flores, C.F. Rosenkrans, Jr. and G.E. Aiken, determined the effects of time of castration on growth, feed-lot performance, and carcass characteristics.

In recent years, we have sought to understand how disparate endocrine and immune signals converge in response to Salmonella enterica serovar Typhimurium (ST) to affect growth and the IGF system in the nursery pig. The enteric pathogen ST interacts with gut epithelium to rapidly upregulate the chemoattractive chemokines IL-8 and chemokine ligand-20, and to selectively affect toll-like receptors. Activation of these components of the innate immune system seems to confine the immune response largely to the gut mucosa and mesenteric lymph nodes, as evidenced by the lack of systemic elevation of proinflammatory cytokines. Despite the apparent restriction of proinflammatory signals to the gut-associated lymphoid tissue, ST provokes peripheral sequelae consistent with danger signaling, including the febrile response and activation of the adrenal axis. In addition, pigs undergoing ST-induced febrile responses experience a consistent period of inappetence that is independent of changes in leptin. Moreover, this period of decreased intake is invariably accompanied by an unmistakable decrease in serum IGF-I and, less consistently, with parallel reductions in circulating IGFBP-3. More recently, we characterized changes in expression of components of the IGF system within skeletal muscle of pigs undergoing ST-associated enteric disease. Despite the characteristic decrease in circulating IGF-I, the relative abundance of skeletal muscle IGF-I and IGFBP-3 mRNA was unaffected by ST. However, mRNA for IGFBP-5 was decreased in the skeletal muscle of ST-challenged pigs, suggesting a possible effect of the enteric disease on IGF availability. Taken together, oral challenge with ST engages elements of the mucosal innate immune system that seem to contain the spread of systemic proinflammatory cytokine signals. Even so, ST challenge is associated with parallel changes in both systemic and local IGF systems that may affect pig growth. [ABSTRACT FROM AUTHOR]

Presents abstracts of studies about the growth and development of the study of animal science. "Body Protein Deposition Response Following Sudden Changes in Ideal Protein Intake Differs Between Pig Types," by H.R. Mart&icute;nez and C.F.M. de Lange; "Human Somatotropin Is More Efficacious Than Porcine Somatotropin in Growing Pigs," by F.R. Dunshea; "Concentrations of Insulin-Like Growth Factors I and II in Embryonic Fluids of Chickens, Ducks and Turkeys," by D.M. Karcher, J.P. McMurtry and T.J. Applegate.

This study was intended to examine whether serum IGF-I concentration is appropriate for use as a physiological predictor for genetic improvement of meat production and meat quality traits in pigs. Heritabilities and genetic correlations were estimated for these traits. The Duroc breed used in this study was selected for seven generations for average daily BW gain (DG) from 30 to 105 kg of BW, loin-eye muscle area (EM), backfat thickness (BF), and intramuscular fat (IMF) content. Serum IGF-I concentration of boars and gilts at the fourth generation of selection and that of boars, gilts, and barrows from the fifth to seventh generations of selection were measured at 8 wk (IGFI-8W) for 832 animals and again at the time they reached 105 kg of BW (IGFI-105KG) for 834 animals. A multivariate REML procedure was used to estimate genetic parameters with a model incorporating generation of selection, sex, common environmental effect of litter, and individual additive genetic effects. Heritability estimates for IGFI-8W and IGFI-105KG were 0.23 ± 0.02 and 0.26 ± 0.03, respectively. The estimates of common environmental effect for IGFI-8W and IGFI-105KG were 0.20 ± 0.02 and 0.03 ± 0.01, respectively. Positive genetic correlations were estimated between IGFI-8W and DG (0.26 ± 0.08), EM (0.22 ± 0.10), and IMF (0.32 ± 0.10). Moreover, the positive genetic correlation between IGFI-105KG and EM was 0.42 ± 0.08. These results indicate that serum IGF-I concentration at an early stage of growth was effective for prediction of IMF, but it was not a reliable physiological predictor of genetic merit of meat production traits. [ABSTRACT FROM AUTHOR]

The discovery in 1922 that an alkaline extract of the anterior pituitary can increase growth and change carcass composition of rats led to the discovery of growth hormone (somatotropin, ST). Since the early studies, much has been learned about the biological effects of ST. The advent of recombinant DNA technology has led to the commercial development of ST-based products for animal agriculture. Administration of porcine ST (pST) at maximally effective doses (approximately 100 μg•kg BW−1•d−1) to growing pigs for 30 to 77 d increases average daily gain approximately 10 to 20%, improves productive efficiency (i.e., the ratio of body weight gain to feed consumed) 13 to 33%, decreases lipid accretion rates by as much as approximately 80%, and stimulates protein deposition (muscle growth) by as much as 70%. These responses are associated with a decrease in feed intake of approximately 10 to 15%. The effects of ST are mediated directly and indirectly. The indirect effects of ST are mediated by the somatomedin (insulin-like growth factor-I). The discovery of somatomedin led to the introduction of the somatomedin hypothesis, which explained the basis of ST action. Since the discovery of the somatomedins, there have been several modifications of the hypothesis developed to accommodate the evolution in understanding of how ST and IGF-I affect a diverse array of biological events. This review will summarize the history of ST and the evolution of the somatomedin hypothesis. [ABSTRACT FROM AUTHOR]

Infections direct amino acids away from growth and skeletal muscle accretion toward the hepatic synthesis of acute-phase proteins. The loss of skeletal muscle protein stores results in both a decrease in muscle function and an increase in mortality. In general, muscle protein synthesis is decreased in rodent models of sepsis, as well as after the injection of components of the bacterial cell wall, such as lipopolysaccharide. Although the overexpression of proinflammatory cytokines is known to hasten the loss of skeletal muscle protein, it is not known whether this represents a direct effect of cytokines or results from secondary changes in the IGF system. Plasma concentrations of IGF-I are dramatically lowered by infection in rats, mice, pigs, and steers. The drop in IGF-I often occurs despite an increase in the plasma concentration of somatotropin. Animals are therefore considered to be GH resistant. The IGF bioactivity is determined not only by the plasma concentration of the ligand, but also by IGFBP; IGFBP-3 is the most abundant of these binding proteins and undergoes proteolysis during some catabolic states. In contrast to IGFBP-3, the plasma concentration of inhibitory IGFBP, such as IGFBP-1, is increased during infection. Insulin-like growth factor-binding protein-1 accumulates in skeletal muscle, where it can potentially inhibit IGF-dependent protein synthesis. Insulin-like growth factor-I and IGFBP-1 are regulated at the level of gene transcription by proinflammatory cytokines. Recent studies demonstrate that bacterial components that activate immune cells also activate the innate immune response in skeletal muscle. Lipopolysaccharide increases proinflammatory cytokine messenger RNA expression in muscle from control mice, but not from mice with a mutation in the lipopolysaccharide receptor. Lipopolysaccharide also increases cytokine expression in human and mouse myoblasts. Local expression of cytokines in skeletal muscle may negatively regulate the autocrine synthesis of IGF-I. Current work is focused on deciphering the mechanism by which muscle becomes GH resistant and the development of therapies to maintain muscle protein stores during infection. [ABSTRACT FROM AUTHOR]

The establishment of in vitro fertilization and culture systems for mammalian embryos has facilitated the application of embryo technologies in research, industry, and clinical settings. Furthermore, the advent of cloning by nuclear transfer has significantly enhanced the potential for genetic modification of livestock. Based on studies in cattle, sheep, and mice, it has become apparent that embryos produced using these systems can differ in morphology and developmental potential compared with embryos produced in vivo. Referred to as "large offspring syndrome," these abnormalities in the development of fetuses, placentas, and offspring are particularly evident following transfer of cloned embryos, but they also occur in pregnancies from embryos produced using in vitro culture alone. The objective of this review is to examine the effects of in vitro production and cloning on bovine embryo and fetal development. Literature pertaining to preimplantation embryo, conceptus, and fetal development, as well as gene expression occurring at each of these three stages, is reviewed. Physiologic and genetic mechanisms that contribute to large offspring syndrome also are discussed. [ABSTRACT FROM AUTHOR]

To determine the influence of three levels of undegradable intake protein (UIP) supplementation on metabolic and endocrine factors that influence reproduction, 23 yearling crossbred heifers (body condition score = 4.5 ± 0.5; initial BW = 362 ± 12 kg) were stratified by BW and assigned randomly to one of three supplements: 1) low UIP (1,135 g·heifer[sup -1]·d[sup -1]; 30% CP, 115 g UIP, n = 7); 2) mid UIP (1,135 g·heifer[sup -1]·d[sup -1]; 38% CP, 216 g UIP, n = 8); or 3) high UIP (1,135 g.heifer[sup -1] ·d[sup -1]; 46% CP, 321 g UIP, n = 8). Heifers were estrually synchronized before initiation of supplementation. Supplement was individually fed daily for 30 to 32 d, at which time heifers were slaughtered (d 12 to 14 of the estrous cycle) and tissues collected. Heifers were fed a basal diet of sudan grass hay (6.0% CP) ad libitum. On d 28 of supplementation (d 10 of the estrous cycle), no differences were observed (P > 0.10) in serum insulin or IGF-I among treatments. At slaughter (d 10 to 12 of the estrous cycle), treatments did not influence corpus luteum weight, cerebral spinal fluid leptin, or IGFBP; serum estradiol-17β, progesterone, leptin, IGF-I, and IGFBP; or anterior pituitary content of IGFBP (P > 0.10). Follicular fluid IGFBP-2 and IGFBP-4 were greater in high-UIP heifers than low- or mid-UIP heifers on d 12 to 14 of the estrous cycle (P < 0.05). Basal serum LH concentrations and LH area under the curve (every 15 min for 240 min) did not differ (P > 0.10) following 28 d of supplementation (d 10 of the estrous cycle); however, basal serum FSH concentrations were greater (P = 0.06) in low- and mid- vs. high-UIP heifers (5.2 and 5.2 vs. 4.6 ng/mL, respectively), and FSH area under the curve was greater (P = 0.03) in low- vs. high-UIP heifers. At slaughter (d 12 to 14 of the estrous cycle), anterior pituitary LH and FSH content and steady-state mRNA encoding α, LHβ, and GnRH receptor did not differ (P > 0.10) among treatments. However, FSHβ mRNA was increased approximately twofold (P = 0.03) in mid vs. low UIP. In summary, low and mid levels of UIP supplements fed to estrous cycling beef heifers seemed to enhance pituitary expression and]or secretion of FSH relative to high levels of UIP. Moreover, high-UIP supplementation was associated with increased low-molecular-weight IGFBP compared with supplementation of low and mid levels of UIP. These data suggest that differing levels of UIP supplementation may alter pituitary and ovarian function, thereby influencing reproductive performance in beef heifers. [ABSTRACT FROM AUTHOR]

The influences of body condition score (BCS) at calving and postpartum nutrition on endocrine and ovarian functions, and reproductive performance, were determined by randomly allocating thin (mean BCS = 4.4 ± 0.1) or moderate condition (mean BCS = 5.1 ± 0.1) Angus × Hereford primiparous cows to receive one of two nutritional treatments after calving. Cows were fed to gain either 0.45 kg/d (M, n = 17) or 0.90 kg/ d (H, n = 17) for the first 71 ± 3 d postpartum. All cows were then fed the M diet until 21 d after the first estrus. A replication (yr 2; M, n = 25; H, n = 23) was also used to evaluate reproductive characteristics. Concentrations of IGF-I, leptin, insulin, glucose, NEFA, and thyroxine were quantified in plasma samples collected weekly during treatment and during 7 wk before the first estrus. Estrous behavior was detected by radiotelemetry, and luteal activity was determined based on concentrations of progesterone in plasma. All cows were bred by AI between 14 and 20 h after onset of estrus, and pregnancy was assessed at 35 to 55 d after AI by ultrasonography. Cows that calved with a BCS of 4 or 5 had similar endocrine function and reproductive performance at the first estrus. During treatment, H cows gained BW and increased BCS (P < 0.01), and had greater (P < 0.05) concentrations of IGF-I, leptin, insulin, glucose, and thyroxine in plasma than M cows. However, during the 7 wk before the first estrus, plasma concentrations of IGF-I, leptin, insulin, glucose, NEFA, and thyroxine were not affected by time. Cows previously on the H treatment had a shorter (P < 0.01) interval to first postpartum estrus and ovulation, and a larger dominant follicle (P < 0.01) at first estrus, than M cows, but duration of estrus and the number of mounts received were not influenced by nutrient intake. Pregnancy rate at the first estrus was greater (P < 0.03) for H (76%, n = 38) than for M (58%, n = 33) cows. Increased nutrient intake after calving stimulated secretion of anabolic hormones, promoted fat deposition, shortened the postpartum interval to estrus, and increased pregnancy rate at the first estrus. Concentrations of IGF-I and leptin in plasma were constant during 7 wk before the first estrus, indicating that acute changes in these hormones are not associated with the resumption of ovarian function in primiparous beef COWS. [ABSTRACT FROM AUTHOR]

We evaluated effects of a 5% (dry matter basis) ground flaxseed supplement (flax) and a trenbolone acetate and estradiol-17β implant, Revalor-S, on circulating IGF-I and muscle IGF-I messenger RNA (mRNA). Sixteen crossbred yearling steers (initial BW = 397 kg) were assigned randomly to one of four treatments: 1) flax/implant; 2) nonflax/implant; 3) flax/nonimplant; and 4) nonflax/nonimplant. Serum was harvested from blood collected on d 0 (before implant or flax addition), 14, and 28, and used in subsequent analyses of circulating IGF-I. Biopsy samples (0.5 g) were obtained from the longissimus muscle on d 0, 14, and 28. Total RNA was isolated from the muscle samples, and real-time quantitative-PCR was used to assess relative differences in IGF-I mRNA. Flax supplementation had no effect (P > 0.10) on circulating IGF-I concentrations. Following implantation, sera from implanted steers had 52 and 84% greater (P < 0.05) IGF-I concentrations than sera from nonimplanted steers on d 14 and 28, respectively. On d 28, local muscle IGF-I mRNA levels increased 2.4-fold (P < 0.01) in biopsy samples obtained from implanted compared with nonimplanted steers. Muscle biopsy samples from nonflax cattle had 4.4-fold higher (P < 0.01) levels of IGF-I mRNA than those from flax cattle on d 28. To determine whether a component of flax, α-linolenic acid (αLA), was directly responsible for IGF-I mRNA down-regulation, we incubated primary cultures of bovine satellite cells, from implanted and nonimplanted steers, in two concentrations of αLA (10 nM and 1 µM). An implant × dose interaction (P < 0.05) was observed for IGF-I mRNA concentrations in bovine satellite cells cultured for 72 h with αLA. Satellite cells from nonimplanted steers had similar (P > 0.10) IGF-I mRNA concentration regardless of the level αLA exposure; however, satellite cells from implanted steers exposed to 10 nM and 1 µM αLA had 2.5- and 2.0-fold greater IGF-I mRNA levels, respectively, than cells from implanted steers that were not exposed to αLA (P < 0.05). Administration of a Revalor-S implant increased circulating IGF-I and local muscle IGF-I mRNA concentrations in finishing cattle. However, muscle IGF-I mRNA levels were decreased by flax supplementation. Muscle cell culture experiments suggested that αLA was not responsible for the IGF-I mRNA down-regulation. [ABSTRACT FROM AUTHOR]

Studies in humans have found circadian changes to be one of the most important sources of controllable preanalytical variability when evaluating bone cell activity using biochemical markers. It remains unclear whether similar circadian changes influence bone marker concentrations in the horse. The aim of this study was to characterize changes in serum concentrations of three biochemical markers of bone cell activity over a 24-h period in six 2-yr-old Thoroughbred mares, and to determine circadian variability in IGFI, which regulates bone turnover. Three bone markers were measured in serum: osteocalcin, a marker of bone formation, the carboxy-terminal propeptide of type-I collagen (a marker of bone formation), and the carboxyterminal telopeptide of type-I collagen (a marker of bone resorption). Data were analyzed using the cosinor technique, which fits a 24-h cycle to each dataset. A significant circadian rhythm was observed for osteocalcin (P = 0.028), with an estimated amplitude of 7.6% of the mean (95% confidence interval 1.3% to 16.3%), and an estimated peak time of 0900. However, the observed rhythm for the carboxy-terminal telopeptide of type-I collagen (amplitude = 7.4%) was not significant (P = 0.067), and there were no significant changes in concentrations of the carboxy-terminal propeptide of type-I collagen over the 24-h study period (P = 0.44). There was a small but significant circadian rhythm for IGFI (P = 0.04), with an estimated amplitude of 3.4% (95% confidence interval 0.2 to 7.1%) and peak at 1730. Further studies are now required to determine the potential association between circadian changes in IGF-I and osteocalcin in the horse. Although no significant circadian variation was found in concentrations of the carboxy-terminal propeptide of type-I collagen and the carboxy-terminal telopeptide of type-I collagen, this may in part be a result of the age of the animals that were still skeletally immature. Future studies should aim to determine whether these markers develop a circadian rhythm at a later age when growth is complete. In the meantime, consistency in time of sampling should continue to be considered best practice when measuring biochemical markers of bone turnover in the horse. [ABSTRACT FROM AUTHOR]

The somatotropic axis and insulin are involved in pre- and post-natal development. In pre- and full-term calves (GrPo and GrNo; born after 277 and 290 d of pregnancy, respectively) and in preterm calves on d 8 of life after being fed for 7 d (GrPs), we studied whether there are differences in the abundance of messenger RNA (mRNA) of IGF-I and IGF-II and of receptors for GH, IGF-I, IGF-II, and insulin among different intestinal sites (duodenum, jejunum, ileum, and colon) and whether there are ontogenetic differences during the perinatal period in intestine and liver. Intestinal site differences (P < 0.05) existed in mRNA levels of IGF-I and IGF-II and receptors for GH, IGF-I, IGF-II, and insulin. Abundance of mRNA of IGF-I and -II and of receptors for IGF-I and GH was highest (P < 0.05) in the colon, abundance of the receptor for IGF-II was comparably high in the colon and ileum, and that of the receptor for insulin was similarly high in colon, ileum, and jejunum. Among GrP[sub 0], GrN[sub 0], and GrP[sub 8] groups, there were differences (P < 0.05) in mRNA levels of IGF-I and IGF-II and of receptors for GH, IGF-I, IGF-II and insulin. Abundance of mRNA of IGF-I and IGF-II and of receptors for GH, IGF-I, IGF-II and insulin was highest (P < 0.05) in GrP[sub 0] calves immediately after birth and was primarily seen in the ileum. In liver, the mRNA levels differed (P < 0.05) among groups for IGF-II and receptors for IGF-I, IGF-II, and insulin, and were highest (P < 0.05) for IGF-II in GrP[sub 0], for receptors of IGF-I in GrN[sub 0], and were higher (P < 0.05) in GrP[sub 0] than GrP[sub 8] for receptors of IGF-II. In conclusion, mRNA levels of IGF-I and IGF-II and of receptors for GH, IGF-I, IGF-II, and insulin were different at different intestinal sites and in intestine and liver and changed during the perinatal period. [ABSTRACT FROM AUTHOR]

This study was conducted to identify polymorphisms in the promoter and coding regions of the bovine growth hormone and growth hormone receptot genes and to study association of polymorphisms identified in these genes with growth traits and serum insulin-like growth factor-I (IGF-I) concentration. The denaturing gradient gel electrophoresis method and sequencing were utilized to identify three new single nucleotide polymorphisms in the promoter region of the growth hormone gene in Angus cattle. Polymerase chain reaction-based restriction fragment length polymorphism procedures were developed for rapid determination of the single nucleotide polymorphism genotypes in the growth hormone and the growth hormone receptor genes among Angus calves from lines divergently selected for high or low blood serum IGF-I concentration. The IGF-I concentration and growth traits were analyzed using animal models. The single nucleotide polymorphism in the promoter region of the growth hormone receptor gene was associated with serum IGFI concentration on d 42 of the postweaning test and with mean IGF-I concentration. The associated effects of the markers need to be verified in other populations. [ABSTRACT FROM AUTHOR]

Forty-eight barrows were used in a 2 × 6 factorial arrangement to test a hypothesis that feeding a protein-deficient diet affects subsequent growth response by altering the efficiency of protein utilization. Barrows were individually fed either a 9% crude protein (CP) diet or an 18% CP diet from 20 to 30 kg of body weight (BW) (depletion phase). From 30 to 45 kg BW (realimentation phase), pigs were fed one of six experimental diets with CP levels of 11.8, 13.1, 14.3, 15.6, 18.8, and 21.8%. Four pigs were slaughtered at 20 kg BW to determine initial body composition. Four pigs from each treatment in depletion phase (a total of eight) were slaughtered at 30 kg BW, and all pigs from each treatment in realimentation phase (a total of 36) were slaughtered at 45 kg BW for subsequent compositional analysis. Pigs were bled at 20, 30, and 40 kg BW for blood urea nitrogen (BUN), insulin-like growth factor (IGF)-I, and IGF-binding protein (IGFBP) assays. Pigs were given three times the maintenance digestible energy requirement (3 × 120 kcal BW[sup -0.75]·d[sup -1]) in three equal meals daily. The feed allowance was adjusted every 3 d. During the depletion phase, pigs fed the 18% CP diet grew faster and more efficiently (P < 0.01) and gained more (P < 0.01) water and protein than did pigs fed the 9% CP diet. Pigs fed the 18% CP diet showed higher (P < 0.01) BUN values, IGF-I concentrations, and IGFBP ratios than pigs fed the 9% CP diet. During the realimentation phase, pigs fed the 9% CP diet during the depletion phase grew faster (P < 0.05), tended to grow more efficiently (P = 0.066), gained more water (P < 0.01), and tended to gain more protein (P = 0.068) than pigs fed the 18% CP diet during the depletion phase. Pigs fed the 9% CP diet during the depletion phase tended (P = 0.069) to have a higher protein requirement during the realimentation phase than pigs fed the 18% CP diet during the depletion phase. When measured at 40 kg BW, pigs fed the 9% CP... [ABSTRACT FROM AUTHOR]

Evaluates the role of growth hormone (GH) in the regulation of hepatic insulin-like growth factor I (IGF-I) mRNA by using a model of suppressed GH secretion during postnatal growth via immunization against growth hormone-releasing factor (GRF). Measurement of IGF-I mRNA levels; Analysis of plasma IGF-I concentrations; Generation of anti-GRF antibodies in plasma.

Determines the effects of managing unimplanted bulls and implanted steers in an accelerated finishing system on insulin-like growth factor I concentrations, feedlot performance and carcass characteristics. Effect of castration status on performance of early-weaned bulls and steers; Analysis of performance and carcass data; Examination of insulin-like growth factor I concentration status x time interactions.

Determines whether acute administration of E[sub2] to barrows increased serum concentrations of E[sub2] to levels similar to those of adult boars. Comparison of boars and gilts in terms of E[sub2] concentrations; Discussion of feed efficiency and carcass traits; Effect of estradiol on components of the insulin-like growth factor system in sheep.

Presents a study which evaluated a biallelic genetic marker identified in the first promoter region of the bovine insulin-like growth factor I (IGF-I) gene in Angus cattle. Sequence and position of oligonucleotide primers in the IGF-I gene; Discussion on point mutation and marker genotyping; Analysis of the polymorphism identified at the IGF-I locus.

Examines the genetic variations in plasma growth hormone (GH) and insulin-like growth factor (IGF)-I concentrations before and following thyrotropin-releasing hormone stimulation in 11-month old Polish Friesian cattle. Association between stimulated GH release and IGF-I milk production traits in GH gene; Phenotypic and genetic parameters for GH release traits; Effect of Leu/Val polymorphism on GH gene.

Deals with a study which used mammary explants from lactating rats and cows to test the effects of prolactin, growth hormone and insulin-like growth factor-I on signal transducer and activator of transcription-5 activation and protein level. Importance of prolactin in lactogenesis; Materials and methods used in the study; Results and discussion.

Discusses a study which determined whether serum concentrations of steroids, insulin-like growth factor (IGF)-I and relative amounts of serum IGF-binding proteins differ in growing boars, barrows and gilts. Materials and methods; Results; Discussion.

Presents a study which determined the heritability of serum insulin-like growth factor-I (IGF-I) concentration and carcass traits in Angus beef cattle. Estimation of the genetic, phenotypic, and environmental correlations of IGF-I with carcass characteristics of beef cattle; Materials and methods; Results and discussion.

Examines the influence of feeding and endogenous growth hormone secretion on circulating insulin-like growth factor-I in colostrum-deprived newborn pigs. Materials and methods; Results and discussion.

Discusses a study which determined whether an antimicrobially induced (ASP-250) increase in serum insulin-like growth (IGF)-I was the result of differences in feed intake. Average daily gain, feed intake and gain; Concentration of serum IGF-I; Concentrations of serum IGF binding protein; Implication of the study.

Presents information on a study which determined the effects of gender and male castration on circulating levels of insulin-like growth factor-I (IGF-I), IGF-II and IGF-binding protein-3 (IGFBP-3) in pigs. Research design and methodology; Results and discussion.

Focuses on a study which examined the differences in scrotal circumference, sperm motility and percentage of normal sperm cells between two lines of Angus beef cattle selected for blood serum insulin-like growth factor I (IGF-I) concentration. Materials and methods used; Results of the study; Implications.