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Article: Use of Agriculturally Important Animals as Models in Biomedical Research.

Smith, Brandon I / Govoni, Kristen E

Advances in experimental medicine and biology

2021 Volume 1354, Page(s) 315–333

Abstract: Livestock have contributed significantly to advances in biomedicine and offer unique advantages over rodent models. The human is the ideal biomedical model; however, ethical reasons limit the testing of hypotheses and treatments in humans. Rodent models ... ...

Abstract	Livestock have contributed significantly to advances in biomedicine and offer unique advantages over rodent models. The human is the ideal biomedical model; however, ethical reasons limit the testing of hypotheses and treatments in humans. Rodent models are frequently used as alternatives to humans due to size, low cost, and ease of genetic manipulation, and have contributed tremendously to our understanding of human health and disease. However, the use of rodents in translational research pose challenges for researchers due to physiological differences to humans. The use of livestock species as biomedical models can address these challenges as livestock have several similarities to human anatomy, physiology, genetics, and metabolism and their larger size permits collection of more frequent and often larger samples. Additionally, recent advances in genetics in livestock species allow for studies in genomics, proteomics, and metabolomics, which have the added benefit of applications to both humans in biomedical research and livestock in improving production. In this review, we provide an overview of scientific findings using livestock and benefits of each model to the livestock industry and to biomedical research.
MeSH term(s)	Animals ; Biomedical Research ; Genomics ; Livestock ; Metabolomics ; Translational Medical Research
Language	English
Publishing date	2021-11-22
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-3-030-85686-1_16
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Timing of maternal nutrient restriction during mid- to late-gestation influences net umbilical uptake of glucose and amino acids in adolescent sheep.

Trotta, Ronald J / Vasquez-Hidalgo, Manuel A / Smith, Brandon I / Reed, Sarah A / Govoni, Kristen E / Vonnahme, Kimberly A / Swanson, Kendall C

Journal of animal science

2023 Volume 101

Abstract: Previous research demonstrated that maternal nutrient restriction during mid- to late-gestation influenced net umbilical uptakes of glucose and amino acids in sheep. However, it is unclear how the timing and duration of nutrient restriction during mid- ... ...

Abstract	Previous research demonstrated that maternal nutrient restriction during mid- to late-gestation influenced net umbilical uptakes of glucose and amino acids in sheep. However, it is unclear how the timing and duration of nutrient restriction during mid- to late-gestation influences net uterine, uteroplacental, and fetal flux of glucose and amino acids. On day 50 of gestation, 41 adolescent ewe lambs carrying singletons were randomly assigned to one of six dietary treatments: 1) 100% of nutrient requirements from days 50 to 90 of gestation (CON; n = 7); 2) 60% of nutrient requirements (RES; n = 7) from days 50 to 90 of gestation; 3) 100% of nutrient requirements from days 50 to 130 of gestation (CON-CON; n = 6); 4) 100% of nutrient requirements from days 50 to 90 of gestation and 60% of nutrient requirements from days 90 to 130 of gestation (CON-RES; n = 7); 5) 60% of nutrient requirements from days 50 to 90 of gestation and 100% of nutrient requirements from days 90 to 130 of gestation (RES-CON; n = 7); or 6) 60% of nutrient requirements from days 50 to 130 of gestation (RES-RES; n = 7). On day 90 (n = 14) and day 130 (n = 27), intraoperative procedures were performed to evaluate uteroplacental blood flows, collect blood samples, and then ewes were euthanized. Net uterine, uteroplacental, and umbilical fluxes of glucose and amino acids were calculated by multiplying blood flow by the arterial-venous concentration difference. Data from days 90 and 130 were analyzed separately using ANOVA in SAS. Maternal nutrient restriction during mid-gestation increased (P = 0.04) net umbilical glucose uptake but, maternal nutrient restriction during late-gestation decreased (P = 0.02) net umbilical glucose uptake. Net umbilical essential amino acid uptake decreased (P = 0.03) with nutrient restriction during mid-gestation; however, net umbilical uptakes of Phe (P = 0.02), Thr (P = 0.05), Met (P = 0.09), and His (P = 0.08) increased or tended to increase after nutrient restriction during late-gestation. These data demonstrate that net umbilical glucose and amino acid uptakes were influenced by the timing of nutrient restriction during mid- to late-gestation. Elevated net umbilical glucose uptake after mid-gestational nutrient restriction was sustained throughout late-gestation, independent of late-gestational feeding level. Long-term adaptations in umbilical glucose uptake may have implications for prenatal and postnatal growth and development of the offspring.
MeSH term(s)	Pregnancy ; Animals ; Sheep ; Female ; Glucose/metabolism ; Amino Acids/metabolism ; Diet/veterinary ; Nutrients ; Fetus/metabolism ; Placenta/metabolism
Chemical Substances	Glucose (IY9XDZ35W2) ; Amino Acids
Language	English
Publishing date	2023-11-30
Publishing country	United States
Document type	Randomized Controlled Trial, Veterinary ; Journal Article
ZDB-ID	390959-1
ISSN	1525-3163 ; 0021-8812
ISSN (online)	1525-3163
ISSN	0021-8812
DOI	10.1093/jas/skad383
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Article ; Online: Restricted- and over-feeding during gestation decreases growth of offspring throughout maturity.

Tillquist, Nicole M / Reed, Sarah A / Kawaida, Mia Y / Reiter, Amanda S / Smith, Brandon I / Jang, Hyung / Lee, Ji-Young / Lee, Elaine C / Zinn, Steven A / Govoni, Kristen E

Translational animal science

2023 Volume 7, Issue 1, Page(s) txad061

Abstract: To determine the effects of poor maternal nutrition on the growth and metabolism of offspring into maturity, multiparous Dorset ewes pregnant with twins ( ...

Abstract	To determine the effects of poor maternal nutrition on the growth and metabolism of offspring into maturity, multiparous Dorset ewes pregnant with twins (
Language	English
Publishing date	2023-05-31
Publishing country	England
Document type	Journal Article
ISSN	2573-2102
ISSN (online)	2573-2102
DOI	10.1093/tas/txad061
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Article ; Online: CELL BIOLOGY SYMPOSIUM: METABOLIC RESPONSES TO STRESS: FROM ANIMAL TO CELL: Poor maternal nutrition during gestation: effects on offspring whole-body and tissue-specific metabolism in livestock species1,2.

Govoni, Kristen E / Reed, Sarah A / Zinn, Steven A

Journal of animal science

2019 Volume 97, Issue 7, Page(s) 3142–3152

Abstract: ... there is recent evidence of altered metabolism in specific tissues (e.g., muscle, adipose, and liver ...

Abstract	Poor maternal nutrition, both restricted-feeding and overfeeding, during gestation can negatively affect offspring growth, body composition, and metabolism. The effects are observed as early as the prenatal period and often persist through postnatal growth and adulthood. There is evidence of multigenerational effects demonstrating the long-term negative impacts on livestock production. We and others have demonstrated that poor maternal nutrition impairs muscle growth, increases adipose tissue, and negatively affects liver function. In addition to altered growth, changes in key metabolic factors, increased glucose concentrations, insulin insensitivity, and hyperleptinemia are observed during the postnatal period. Furthermore, there is recent evidence of altered metabolism in specific tissues (e.g., muscle, adipose, and liver) and stem cells. The systemic and local changes in metabolism demonstrate the importance of determining the mechanism(s) by which maternal diet programs offspring growth and metabolism in an effort to develop novel management practices to improve the efficiency of growth and health in these offspring.
MeSH term(s)	Adipose Tissue/metabolism ; Animals ; Animals, Newborn ; Body Composition ; Diet/veterinary ; Female ; Liver/metabolism ; Livestock/physiology ; Maternal Nutritional Physiological Phenomena ; Organ Specificity ; Pregnancy ; Prenatal Nutritional Physiological Phenomena ; Stress, Physiological
Language	English
Publishing date	2019-05-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	390959-1
ISSN	1525-3163 ; 0021-8812
ISSN (online)	1525-3163
ISSN	0021-8812
DOI	10.1093/jas/skz157
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Article ; Online: Insulin-like growth factor-I molecular pathways in osteoblasts: potential targets for pharmacological manipulation.

Govoni, Kristen E

Current molecular pharmacology

2012 Volume 5, Issue 2, Page(s) 143–152

Abstract: The insulin-like growth factors (IGFs) are the most abundant growth factors stored in bone and produced by osteoblasts. IGF-I is an important regulator of osteoblast function and required for optimal bone development and maintenance. IGF-I can act in an ... ...

Abstract	The insulin-like growth factors (IGFs) are the most abundant growth factors stored in bone and produced by osteoblasts. IGF-I is an important regulator of osteoblast function and required for optimal bone development and maintenance. IGF-I can act in an endocrine, paracrine or autocrine manner and is regulated by a family of six IGF binding proteins (IGFBPs). The IGFBPs are often found bound to IGF-I in the circulation or complexed with IGF-I in osteoblasts. IGFBP-3 and -5 are known stimulators of IGF-I actions, whereas IGFBP-1, -2, -4 and -6 are known inhibitors of IGF-I action in bone. Once IGF-I binds to its receptor (type 1 IGF receptor) it initiates a complex signaling pathway including the phosphoinositol 3-kinase (PI3-K)/3-PI-dependent kinase (PDK)-1/Akt pathway and the Ras/Raf/mitogen-activated protein (MAP) kinase pathway which stimulate cell function and/or survival. Based on the critical role for IGF-I in osteoblasts, it is a logical candidate for anabolic therapy. However, systemic administration of IGF-I is not cell specific and a limited number of long term experiments have been completed to date. Several recent findings indicate that many of the IGFBPs and specific proteins in the IGF-I signaling pathways are also potent anabolic factors in regulating osteoblast function. This review will focus on the role of these factors in mediating IGF-I action in osteoblasts and how they may serve as potential targets to stimulate osteoblast function and bone formation.
MeSH term(s)	Growth Hormone-Releasing Hormone/metabolism ; Humans ; Insulin-Like Growth Factor Binding Proteins/metabolism ; Insulin-Like Growth Factor I/metabolism ; Osteoblasts/metabolism ; Osteogenesis ; Receptor, IGF Type 1/metabolism ; Signal Transduction
Chemical Substances	Insulin-Like Growth Factor Binding Proteins ; Insulin-Like Growth Factor I (67763-96-6) ; Growth Hormone-Releasing Hormone (9034-39-3) ; Receptor, IGF Type 1 (EC 2.7.10.1)
Language	English
Publishing date	2012-06
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	1874-4702
ISSN (online)	1874-4702
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Article ; Online: Understanding gestational and feed management practices of New England sheep producers.

Kelly, Miriah R / Halpern, Arielle / Reed, Sarah A / Zinn, Steven A / Govoni, Kristen E

Translational animal science

2021 Volume 5, Issue 1, Page(s) txaa234

Abstract: ... to New England sheep producers via Qualtrics using e-mail survey links, with a 33.2% response rate ( ...

Abstract	Several sources of information are available to producers for guidance in managing their breeding flocks; however, it is unknown if sheep producers utilize any or all of these resources. Because maternal diet during gestation can have immediate and long-lasting negative effects on growth and health of offspring, it is important for producers to insure they are providing appropriate nutritional management to ewes during breeding and gestation. Historically, New England sheep producers have not been included in USDA surveys of sheep producers, and therefore, there is a lack of information about how New England producers manage their flocks, especially in terms of nutrition and gestation. The objective was to determine flock size, breeds, pregnancy detection methods, and feeding management practices of New England sheep producers. To meet this objective, a 12-question survey was developed and disseminated to New England sheep producers via Qualtrics using e-mail survey links, with a 33.2% response rate (
Language	English
Publishing date	2021-01-03
Publishing country	England
Document type	Journal Article
ISSN	2573-2102
ISSN (online)	2573-2102
DOI	10.1093/tas/txaa234
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Article: Maternal Overnutrition During Gestation in Sheep Alters Autophagy Associated Pathways in Offspring Heart.

Liu, Yang / Ding, Qiyue / Halderson, Steven J / Arriola Apelo, Sebastian I / Jones, Amanda K / Pillai, Sambhu M / Hoffman, Maria L / Reed, Sarah / Govoni, Kristen E / Zinn, Steven A / Guo, Wei

Frontiers in genetics

2022 Volume 12, Page(s) 742704

Abstract: Poor maternal nutrition during gestation can negatively affect offspring growth, development, and health pre- and post-natally. Overfeeding during gestation or maternal obesity (MO) results in altered metabolism and imbalanced endocrine hormones in ... ...

Abstract	Poor maternal nutrition during gestation can negatively affect offspring growth, development, and health pre- and post-natally. Overfeeding during gestation or maternal obesity (MO) results in altered metabolism and imbalanced endocrine hormones in animals and humans which will have long-lasting and detrimental effects on offspring growth and health. In this study, we examined the effects of overnutrition during gestation on autophagy associated pathways in offspring heart muscles at two gestational and one early postnatal time point (
Language	English
Publishing date	2022-01-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2021.742704
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Article ; Online: Poor maternal diet during gestation alters offspring muscle proteome in sheep.

Reed, Sarah A / Balsbaugh, Jeremy / Li, Xiaomeng / Moore, Timothy E / Jones, Amanda K / Pillai, Sambhu M / Hoffman, Maria L / Govoni, Kristen E / Zinn, Steven A

Journal of animal science

2022 Volume 100, Issue 8

Abstract: Poor maternal nutrition during gestation can result in reduced offspring muscle growth and altered muscle metabolism. We hypothesized that over- or restricted-nutrition during gestation would alter the longissimus dorsi muscle (LM) proteome of offspring. ...

Abstract	Poor maternal nutrition during gestation can result in reduced offspring muscle growth and altered muscle metabolism. We hypothesized that over- or restricted-nutrition during gestation would alter the longissimus dorsi muscle (LM) proteome of offspring. Pregnant ewes were fed 60% (restricted), 100% (control), or 140% (over) of National Research Council requirements for total digestible nutrients from day 30 of gestation until parturition. Fetal (RES, CON, OVER) LM were collected at days 90 and 135 of gestation, or from offspring within 24 h of birth. Sarcoplasmic proteins were isolated, trypsin digested, and subjected to multiplexed, label-based quantitative mass spectrometry analysis integrating tandem mass tag technology. Differential expression of proteins was identified by ANOVA followed by Tukey's HSD post hoc tests, and regularized regression via the elastic net. Significance was set at P < 0.05. Over-represented pathways containing differentially expressed proteins were identified by Reactome and included metabolism of proteins, immune system, cellular response to stress/external stimuli, developmental biology, and infectious disease. As a result of maternal diet, a total of 312 proteins were differentially expressed (day 90 = 89 proteins; day 135 = 115 proteins; birth = 131 proteins). Expression of eukaryotic initiation factor (EIF) 2S3, EIF3L, and EIF4G2 was lower in OVER fetuses at day 90 of gestation (P < 0.05). Calcineurin A and mitogen-activated protein kinase 1 were greater in RES fetuses at day 90 (P < 0.04). At day 135 of gestation, pyruvate kinase and lactate dehydrogenase A expression were greater in OVER fetuses than CON (P < 0.04). Thioredoxin expression was greater in RES fetuses relative to CON at day 135 (P = 0.05). At birth, proteins of the COP9 signalosome complex were greater in RES offspring relative to OVER (P < 0.05). Together, these data indicate that protein degradation and synthesis, metabolism, and oxidative stress are altered in a time and diet-specific manner, which may contribute to the phenotypic and metabolic changes observed during fetal development and postnatal growth.
MeSH term(s)	Animal Nutritional Physiological Phenomena ; Animals ; Diet/veterinary ; Female ; Maternal Nutritional Physiological Phenomena ; Muscles ; Pregnancy ; Proteome ; Sheep
Chemical Substances	Proteome
Language	English
Publishing date	2022-07-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	390959-1
ISSN	1525-3163 ; 0021-8812
ISSN (online)	1525-3163
ISSN	0021-8812
DOI	10.1093/jas/skac061
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Article ; Online: Maternal nutrient restriction and over-feeding during gestation alter expression of key factors involved in placental development and vascularization.

Reed, Sarah A / Ashley, Ryan / Silver, Gail / Splaine, Caitlyn / Jones, Amanda K / Pillai, Sambhu M / Peterson, Maria L / Zinn, Steven A / Govoni, Kristen E

Journal of animal science

2022 Volume 100, Issue 6

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Animals ; Female ; Nutrients ; Placenta/metabolism ; Placentation ; Pregnancy ; RNA, Messenger/metabolism ; Sheep ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism ; Vascular Endothelial Growth Factor A/metabolism
Chemical Substances	RNA, Messenger ; Vascular Endothelial Growth Factor A ; TOR Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2022-06-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	390959-1
ISSN	1525-3163 ; 0021-8812
ISSN (online)	1525-3163
ISSN	0021-8812
DOI	10.1093/jas/skac155
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Article ; Online: Poor maternal nutrition during gestation in sheep alters prenatal muscle growth and development in offspring.

Gauvin, Mary C / Pillai, Sambhu M / Reed, Sarah A / Stevens, John R / Hoffman, Maria L / Jones, Amanda K / Zinn, Steven A / Govoni, Kristen E

Journal of animal science

2020 Volume 98, Issue 1

Abstract: Poor maternal nutrition during gestation can have immediate and life-long negative effects on offspring growth and health. In livestock, this leads to reduced product quality and increased costs of production. Based on previous evidence that both ... ...

Abstract	Poor maternal nutrition during gestation can have immediate and life-long negative effects on offspring growth and health. In livestock, this leads to reduced product quality and increased costs of production. Based on previous evidence that both restricted- and overfeeding during gestation decrease offspring muscle growth and alter metabolism postnatally, we hypothesized that poor maternal nutrition during gestation would reduce the growth and development of offspring muscle prenatally, reduce the number of myogenic progenitor cells, and result in changes in the global expression of genes involved in prenatal muscle development and function. Ewes were fed a control (100% NRC)-, restricted (60% NRC)-, or overfed (140% NRC) diet beginning on day 30 of gestation until days 45, 90, and 135 of gestation or until parturition. At each time point fetuses and offspring (referred to as CON, RES, and OVER) were euthanized and longissimus dorsi (LM), semitendinosus (STN), and triceps brachii (TB) were collected at each time point for histological and RNA-Seq analysis. In fetuses and offspring, we did not observe an effect of diet on cross-sectional area (CSA), but CSA increased over time (P < 0.05). At day 90, RES and OVER had reduced secondary:primary muscle fiber ratios in LM (P < 0.05), but not in STN and TB. However, in STN and TB percent PAX7-positive cells were decreased compared with CON (P < 0.05). Maternal diet altered LM mRNA expression of 20 genes (7 genes downregulated in OVER and 2 downregulated in RES compared with CON; 5 downregulated in OVER compared with RES; false discovery rate (FDR)-adj. P < 0.05). A diet by time interaction was not observed for any genes in the RNA-Seq analysis; however, 2,205 genes were differentially expressed over time between days 90 and 135 and birth (FDR-adj. P < 0.05). Specifically, consistent with increased protein accretion, changes in muscle function, and increased metabolic activity during myogenesis, changes in genes involved in cell cycle, metabolic processes, and protein synthesis were observed during fetal myogenesis. In conclusion, poor maternal nutrition during gestation contributes to altered offspring muscle growth during early fetal development which persists throughout the fetal stage. Based on muscle-type-specific effects of maternal diet, it is important to evaluate more than one type of muscle to fully elucidate the effects of maternal diet on offspring muscle development.
MeSH term(s)	Animal Nutritional Physiological Phenomena/genetics ; Animals ; Diet/veterinary ; Down-Regulation/genetics ; Female ; Fetal Development/genetics ; Gene Expression Regulation, Developmental ; Humans ; Immunohistochemistry/veterinary ; Male ; Maternal Nutritional Physiological Phenomena/genetics ; Muscle Development/genetics ; Muscle, Skeletal/embryology ; Pregnancy ; Sequence Analysis, RNA/veterinary ; Sheep/embryology ; Sheep/genetics ; Sheep/physiology ; Time Factors ; Up-Regulation/genetics ; Vitamins/administration & dosage
Chemical Substances	Vitamins
Language	English
Publishing date	2020-01-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	390959-1
ISSN	1525-3163 ; 0021-8812
ISSN (online)	1525-3163
ISSN	0021-8812
DOI	10.1093/jas/skz388
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