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| 1 | Functional roles of ornithine decarboxylase and arginine decarboxylase during the peri-implantation period of pregnancy in sheep显示文摘Background: Polyamines stimulate DNA transcription and m RNA translation for protein synthesis in trophectoderm cells, as well as proliferation and migration of cells; therefore, they are essential for development and survival of conceptuses(embryo/fetus and placenta). The ovine conceptus produces polyamines via classical and non-classical pathways. In the classical pathway, arginine(Arg) is transformed into ornithine, which is then decarboxylated by ornithine decarboxylase(ODC1) to produce putrescine which is the substrate for the production of spermidine and spermine. In the non-classical pathway, Arg is converted to agmatine(Agm) by arginine decarboxylase(ADC), and Agm is converted to putrescine by agmatinase(AGMAT).Methods: Morpholino antisense oligonucleotides(MAOs) were designed and synthesized to inhibit translational initiation of the m RNAs for ODC1 and ADC, in ovine conceptuses.Results: The morphologies of MAO control, MAO-ODC1, and MAO-ADC conceptuses were normal. Double knockdown of ODC1 and ADC(MAO-ODC1:ADC) resulted in two phenotypes of conceptuses; 33% of conceptuses appeared to be morphological y and functional y normal(phenotype a) and 67% of the conceptuses presented an abnormal morphology and functionality(phenotype b). Furthermore, MAO-ODC1:ADC(a) conceptuses had greater tissue concentrations of Agm,putrescine, and spermidine than MAO control conceptuses, while MAO-ODC1:ADC(b) conceptuses only had greater tissue concentrations of Agm. Uterine flushes from ewes with MAO-ODC1:ADC(a) had greater amounts of arginine, aspartate, tyrosine, citrulline, lysine, phenylalanine, isoleucine, leucine, and glutamine, while uterine flushes of ewes with MAO-ODC1:ADC(b) conceptuses had lower amount of putrescine, spermidine, spermine, alanine, aspartate,glutamine, tyrosine, phenylalanine, isoleucine, leucine, and lysine.Conclusions: The double-knockdown of translation of ODC1 and ADC m RNAs was most detrimental to conceptus development and their production of interferon tau(IFNT). Agm, polyamines, amino acids, and adequate secretion of IFNT are critical for establishment and maintenance of pregnancy during the peri-implantation period of gestation in sheep. | Yasser Y.Lenis Gregory A.Johnson Xiaoqiu Wang Wendy W.Tang Kathrin A.Dunlap M.Carey Satterfield Guoyao Wu Thomas R.Hansen Fuller W.Bazer | 2018 | Journal of Animal Science and Biotechnology2018，9，2： | 3 |
| 2 | Pre-implantation exogenous progesterone and pregnancy in sheep.II.Effects on fetalplacental development and nutrient transporters in late pregnancy显示文摘Background:Administration of progesterone(P4)to ewes during the first 9 to 12 days of pregnancy accelerates blastocyst development by day 12 of pregnancy,likely due to P4-induced up-regulation of key genes in uterine epithelia responsible for secretion and transport of components of histotroph into the uterine lumen.This study determined if acceleration of blastocyst development induced by exogenous P4 during the pre-implantation period affects fetal-placental development on day 125 of pregnancy.Suffolk ewes(n=35)were mated to fertile rams and assigned randomly to receive daily intramuscular injections of either corn oil vehicle(CO,n=18)or 25 mg progesterone in CO(P4,n=17)for the first 8 days of pregnancy.All ewes were hysterectomized on day 125 of pregnancy and:1)fetal and placental weights and measurements were recorded;2)endometrial and placental tissues were analyzed for the expression of candidate mRNAs involved in nutrient transport and arginine metabolism;and 3)maternal plasma,fetal plasma,allantoic fluid,and amniotic fluid were analyzed for amino acids,agmatine,polyamines,glucose,and fructose.Results:Treatment of ewes with exogenous P4 did not alter fetal or placental growth,but increased amounts of aspartate and arginine in allantoic fluid and amniotic fluid,respectively.Ewes that received exogenous P4 had greater expression of mRNAs for SLC7A1,SLC7A2,SLC2A1,AGMAT,and ODC1 in endometria,as well as SLC1A4,SLC2A5,SLC2A8 and ODC1 in placentomes.In addition,AZIN2 protein was immunolocalized to uterine luminal and glandular epithelia in P4-treated ewes,whereas AZIN2 localized only to uterine luminal epithelia in CO-treated ewes.Conclusions:This study revealed that exogenous P4 administered in early pregnancy influenced expression of selected genes for nutrient transporters and the expression of a protein involved in polyamine synthesis on day 125 of pregnancy,suggesting a‘programming’effect of P4 on gene expression that affected the composition of nutrients in fetal-placental fluids. | Katherine M.Halloran Emily C.Hoskins Claire Stenhouse Robyn M.Moses Kathrin A.Dunlap M.Carey Satterfield Heewon Seo Gregory A.Johnson Guoyao Wu Fuller W.Bazer | 2021 | Journal of Animal Science and Biotechnology2021，12，3： | 1 |
| 3 | Spatial relation between microbleeds and amyloid deposits in amyloid angiopathy显示文摘 | Gregory A.Dierksen Maureen E.Skehan Muhammad A.Khan JedJeng R.N. KaveerNandigam John A.Becker AshokKumar Krista L.Neal Rebecca A.Betensky Matthew P.Frosch JonathanRosand Keith A.Johnson AnandViswanathan David H.Salat Steven M.Greenberg | 2010 | Ann Neurol2010，，4： | 1 |
| 4 | Integrins and their potential roles in mammalian pregnancy显示文摘Integrins are a highly complex family of receptors that, when expressed on the surface of cells, can mediate reciprocal cell-to-cell and cell-to-extracellular matrix(ECM) interactions leading to assembly of integrin adhesion complexes(IACs) that initiate many signaling functions both at the membrane and deeper within the cytoplasm to coordinate processes including cell adhesion, migration, proliferation, survival, differentiation, and metabolism. All metazoan organisms possess integrins, and it is generally agreed that integrins were associated with the evolution of multicellularity, being essential for the association of cells with their neighbors and surroundings, during embryonic development and many aspects of cellular and molecular biology. Integrins have important roles in many aspects of embryonic development, normal physiology, and disease processes with a multitude of functions discovered and elucidated for integrins that directly influence many areas of biology and medicine, including mammalian pregnancy, in particular implantation of the blastocyst to the uterine wall, subsequent placentation and conceptus(embryo/fetus and associated placental membranes) development. This review provides a succinct overview of integrin structure, ligand binding, and signaling followed with a concise overview of embryonic development, implantation, and early placentation in pigs, sheep, humans, and mice as an example for rodents. A brief timeline of the initial localization of integrin subunits to the uterine luminal epithelium(LE) and conceptus trophoblast is then presented, followed by sequential summaries of integrin expression and function during gestation in pigs, sheep, humans, and rodents. As appropriate for this journal, summaries of integrin expression and function during gestation in pigs and sheep are in depth, whereas summaries for humans and rodents are brief. Because similar models to those illustrated in Fig. 1, 2, 3, 4, 5 and 6 are present throughout the scientific literature, the illustrations in this manuscript are drafted as Viking imagery for entertainment purposes. | Gregory A.Johnson Robert C.Burghardt Fuller W.Bazer Heewon Seo Joe W.Cain | 2024 | Journal of Animal Science and Biotechnology2024，15，1： | 0 |
| 5 | Dietary supplementation with 0.4%L-arginine between days 14 and 30 of gestation enhances NO and polyamine syntheses and water transport in porcine placentae显示文摘Background:Most embryonic loss in pigs occurs before d 30 of gestation.Dietary supplementation with L-arginine(Arg) during early gestation can enhance the survival and development of conceptuses(embryo/fetus and its extraembryonic membranes) in gilts.However,the underlying mechanisms remain largely unknown.Methods:Between d 14 and 30 of gestation,each gilt was fed daily 2 kg of a corn-and soybean-meal based diet(12% crude protein) supplemented with either 0.4% Arg(as Arg-HCl) or an isonitrogenous amount of L-alanine(Control).There were 10 gilts per treatment group.On d 30 of gestation,gilts were fed either Arg-HCl or L-alanine 30 min before they were hysterectomized,followed by the collection of placentae,embryos,fetal membranes,and fetal fluids.Amniotic and allantoic fluids were analyzed for nitrite and nitrate [NOx;stable oxidation products of nitric oxide(NO)],polyamines,and amino acids.Placentae were analyzed for syntheses of NO and polyamines,water and amino acid transport,concentrations of amino acid-related metabolites,and the expression of angiogenic factors and aquaporins(AQPs).Results:Compared to the control group,Arg supplementation increased(P < 0.05) the number of viable fetuses by 1.9 per litter,the number and diameter of placental blood vessels(+ 25.9% and + 17.0% respectively),embryonic survival(+ 18.5%),total placental weight(+ 36.5%),the total weight of viable fetuses(+ 33.5%),fetal crown-to-rump length(+ 4.7%),and total allantoic and amniotic fluid volumes(+ 44.6% and + 75.5% respectively).Compared to control gilts,Arg supplementation increased(P < 0.05) placental activities of GTP cyclohydrolase-1(+ 33.1%) and ornithine decarboxylase(+ 29.3%);placental syntheses of NO(+ 26.2%) and polyamines(+ 28.9%);placental concentrations of NOx(+ 22.5%),tetrahydrobiopterin(+ 21.1%),polyamines(+ 20.4%),c AMP(+ 27.7%),and c GMP(+ 24.7%);total amounts of NOx(+ 61.7% to + 96.8%),polyamines(+ 60.7% to + 88.7%),amino acids(+ 39% to + 118%),glucose(+ 60.5% to + 62.6%),and fructose(+ 41.4% to + 57.0%) in fetal fluids;and the placental transport of water(+ 33.9%),Arg(+ 78.4%),glutamine(+ 89.9%),and glycine(+ 89.6%).Furthermore,Arg supplementation increased(P < 0.05) placental m RNA levels for angiogenic factors [VEGFA120(+ 117%),VEGFR1(+ 445%),VEGFR2(+ 373%),PGF(+ 197%),and GCH1(+ 126%)] and AQPs [AQP1(+ 280%),AQP3(+ 137%),AQP5(+ 172%),AQP8(+ 165%),and AQP9(+ 127%)].Conclusion:Supplementing 0.4% Arg to a conventional diet for gilts between d 14 and d 30 of gestation enhanced placental NO and polyamine syntheses,angiogenesis,and water and amino acid transport to improve conceptus development and survival. | Cassandra M.Herring Fuller W.Bazer Gregory A.Johnson Heewon Seo Shengdi Hu Mohammed Elmetwally Wenliang He Daniel B.Long Guoyao Wu | 2023 | Journal of Animal Science and Biotechnology2023，14，2： | 0 |
| 6 | Pre-implantation exogenous progesterone and pregnancy in sheep:I.polyamines,nutrient transport,and progestamedins显示文摘Background:Administration of exogenous progesterone(P4)to ewes during the pre-implantation period advances conceptus development and implantation.This study determined effects of exogenous P4 on transport of select nutrients and pathways that enhance conceptus development.Pregnant ewes(n=38)were treated with either 25 mg P4 in 1 mL corn oil(P4,n=18)or 1mL corn oil alone(CO,n=20)from day 1.5 through day 8 of pregnancy and hysterectomized on either day 9 or day 12 of pregnancy.Endometrial expression of genes encoding enzymes for synthesis of polyamines,transporters of glucose,arginine,and glycine,as well as progestamedins was determined by RT-qPCR.Results:On day 12 of pregnancy,conceptuses from P4-treated ewes had elongated while those from CO-treated ewes were spherical.The mRNA expression of AZIN2,an arginine decarboxylase,was lower in endometria of P4-treated than CO-treated ewes on day 9 of pregnancy.Expression of FGF10,a progestamedin,was greater in endometria of CO and P4-treated ewes on day 12 of gestation in addition to P4-treated ewes necropsied on day 9 of gestation.Treatment with P4 down-regulated endometrial expression of amino acid transporter SLC1A4 on day 12 of pregnancy.Conclusions:Results indicated that administration of exogenous P4 during the pre-implantation period advanced the expression of FGF10,which may accelerate proliferation of trophectoderm cells,but also was correlated with decreased expression of glycine and serine transporters and polyamine synthesis enzyme AZIN2.Further research with increased sample sizes may determine how differential expression affects endometrial functions and potentially embryonic loss. | Emily C.Hoskins Katherine M.Halloran Claire Stenhouse Robyn M.Moses Kathrin A.Dunlap Michael C.Satterfield Heewon Seo Gregory A.Johnson Guoyao Wu Fuller W.Bazer | 2021 | Journal of Animal Science and Biotechnology2021，12，3： | 0 |
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