The pathophysiological changes associated with neonatal death of cloned pigs

in Reproduction

Correspondence should be addressed to Z Wu or Z Li; Email: wzfemail@163.com or lizicong@scau.edu.cn
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Cloned pigs generated by the somatic cell transfer nuclear (SCNT) technique are highly valuable for agriculture, biomedicine, and life sciences. However, the neonatal mortality rate of cloned pigs is very high. The reasons causing the massive loss of cloned pigs during their neonatal ages are unclear. In the present study, we found that the neonatal death of cloned pigs was associated with aberrant purine metabolism, impaired renal morphology and function, and decreased hepatic Hprt1 expression. The downregulation of Hprt1, a key purine metabolism regulation gene, in the liver was responsible for the elevation of an important purine metabolite, uric acid, in the serum, causing abnormalities in kidney morphology and function and leading to death of neonatal cloned pigs. This study provided insights into the pathophysiological mechanisms underlying the neonatal death of clone pigs, and results will help improve their survival rate.

Supplementary Materials

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  • AhearneCEDenihanNMWalshBHReinkeSNKennyLCBoylanGBBroadhurstDIMurrayDM 2016 Metabolite index and outcome in perinatal asphyxia and hypoxic-ischaemic encephalopathy. Neonatology 110 296302. (https://doi.org/10.1159/000446556)

    • Search Google Scholar
    • Export Citation
  • AhmedMTaylorWSmithPRBeckerMA 1999 Accelerated transcription of PRPS1 in X-linked overactivity of normal human phosphoribosylpyrophosphate synthetase. Journal of Biological Chemistry 274 74827488. (https://doi.org/10.1074/jbc.274.11.7482)

    • Search Google Scholar
    • Export Citation
  • AoZLiZCWangXWZhaoCFGanYMWuXZengFShiJSGuTHongLJ 2019 Identification of amniotic fluid metabolomic and placental transcriptomic changes associated with abnormal development of cloned pig fetuses. Molecular Reproduction and Development 86 278291. (https://doi.org/10.1002/mrd.23102)

    • Search Google Scholar
    • Export Citation
  • AoZLiuDWZhaoCFYueZMShiJSZhouRCaiGYZhengEGLiZCWuZF 2017 Birth weight, umbilical and placental traits in relation to neonatal loss in cloned pigs. Placenta 57 94101. (https://doi.org/10.1016/j.placenta.2017.06.010)

    • Search Google Scholar
    • Export Citation
  • BaxterEMJarvisSD’EathRBRossDWRobsonSKFarishMNevisonIMLawrenceABEdwardsSA 2008 Investigating the behavioural and physiological indicators of neonatal survival in pigs. Theriogenology 69 773783. (https://doi.org/10.1016/j.theriogenology.2007.12.007)

    • Search Google Scholar
    • Export Citation
  • BorghiCRoseiEABardinTDawsonJDominiczakAKielsteinJTManolisAJPerez-RuizFManciaG 2015 Serum uric acid and the risk of cardiovascular and renal disease. Journal of Hypertension 33 1729–1741. (https://doi.org/10.1097/HJH.0000000000000701)

    • Search Google Scholar
    • Export Citation
  • CaoZLiYChenZWangHZhangMZhouNWuRLingYFangFLiN 2015 Genome-wide dynamic profiling of histone methylation during nuclear transfer-mediated porcine somatic cell reprogramming. PLoS ONE 10 e0144897. (https://doi.org/10.1371/journal.pone.0144897)

    • Search Google Scholar
    • Export Citation
  • Ceballos-PicotIMockelLPotierMCDauphinotLShirleyTLTorero-IbadRFuchsJJinnahHA 2009 Hypoxanthine-guanine phosphoribosyl transferase regulates early developmental programming of dopamine neurons: implications for Lesch-Nyhan disease pathogenesis. Human Molecular Genetics 18 23172327. (https://doi.org/10.1093/hmg/ddp164)

    • Search Google Scholar
    • Export Citation
  • CedarHBergmanY 2009 Linking DNA methylation and histone modification: patterns and paradigms. Nature Reviews Genetics 10 295304. (https://doi.org/10.1038/nrg2540)

    • Search Google Scholar
    • Export Citation
  • DehghanAvan HoekMSijbrandsEJHofmanAWittemanJC 2008 High serum uric acid as a novel risk factor for type 2 diabetes. Diabetes Care 31 361362. (https://doi.org/10.2337/dc07-1276)

    • Search Google Scholar
    • Export Citation
  • DhanasekaranSDohertyTMKennethJ & TB Trials Study Group 2010 Comparison of different standards for real-time PCR-based absolute quantification. Journal of Immunological Methods 354 3439. (https://doi.org/10.1016/j.jim.2010.01.004)

    • Search Google Scholar
    • Export Citation
  • EstradaJSommerJCollinsBMirBMartinAYorkAPettersRMPiedrahitaJA 2007 Swine generated by somatic cell nuclear transfer have increased incidence of intrauterine growth restriction (IUGR). Cloning and Stem Cells 9 229236. (https://doi.org/10.1089/clo.2006.0079)

    • Search Google Scholar
    • Export Citation
  • HobbsDJSteinkeJMChungJYBarlettaGMBunchmanTE 2010 Rasburicase improves hyperuricemia in infants with acute kidney injury. Pediatric Nephrology 25 305309. (https://doi.org/10.1007/s00467-009-1352-1)

    • Search Google Scholar
    • Export Citation
  • HongLJHouCYLiXPLiCCZhaoSHYuM 2014 Expression of heparanase is associated with breed-specific morphological characters of placental folded bilayer between Yorkshire and Meishan pigs. Biology of Reproduction 90 56. (https://doi.org/10.1095/biolreprod.113.114181)

    • Search Google Scholar
    • Export Citation
  • HuanYJHuKXieBTShiYQWangFZhouYLiuSCHuangBZhuJLiuZF 2015 Ovulation statuses of surrogate gilts are associated with the efficiency of excellent pig cloning. PLoS ONE 10 e0142549. (https://doi.org/10.1371/journal.pone.0142549)

    • Search Google Scholar
    • Export Citation
  • InoueKKohdaTSugimotoMSadoTOgonukiNMatobaSShiuraHIkedaRMochidaKFujiiT 2010 Impeding Xist expression from the active X chromosome improves mouse somatic cell nuclear transfer. Science 330 496499. (https://doi.org/10.1126/science.1194174)

    • Search Google Scholar
    • Export Citation
  • JiangLLaiLSamuelMPratherRSYangXTianXC 2008 Expression of X-linked genes in deceased neonates and surviving cloned female piglets. Molecular Reproduction and Development 75 265273. (https://doi.org/10.1002/mrd.20758)

    • Search Google Scholar
    • Export Citation
  • JinnahHAVisserJEHarrisJCVerduALarovereLCeballos-PicotIGonzalez-AlegrePNeychevVTorresRJDulacO 2006 Delineation of the motor disorder of Lesch-Nyhan disease. Brain 129 12011217. (https://doi.org/10.1093/brain/awl056)

    • Search Google Scholar
    • Export Citation
  • JohnsonCHIvanisevicJSiuzdakG 2016 Metabolomics: beyond biomarkers and towards mechanisms. Nature Reviews: Molecular Cell Biology 17 451459. (https://doi.org/10.1038/nrm.2016.25)

    • Search Google Scholar
    • Export Citation
  • KanbayMIkizekMSolakYSelcokiYUysalSArmutcuFEryonucuBCovicAJohnsonRJ 2011 Uric acid and pentraxin-3 levels are independently associated with coronary artery disease risk in patients with stage 2 and 3 kidney disease. American Journal of Nephrology 33 325331. (https://doi.org/10.1159/000324916)

    • Search Google Scholar
    • Export Citation
  • KangDHNakagawaTFengLWatanabeSHanLMazzaliMTruongLHarrisRJohnsonRJ 2002 A role for uric acid in the progression of renal disease. Journal of the American Society of Nephrology 13 28882897. (https://doi.org/10.1097/01.asn.0000034910.58454.fd)

    • Search Google Scholar
    • Export Citation
  • KataokaHYangKRockKL 2015 The xanthine oxidase inhibitor febuxostat reduces tissue uric acid content and inhibits injury-induced inflammation in the liver and lung. European Journal of Pharmacology 746 174179. (https://doi.org/10.1016/j.ejphar.2014.11.013)

    • Search Google Scholar
    • Export Citation
  • KuromeMGeistlingerLKesslerBZakhartchenkoVKlymiukNWuenschARichterABaehrAKraeheKBurkhardtK 2013 Factors influencing the efficiency of generating genetically engineered pigs by nuclear transfer: multi-factorial analysis of a large data set. BMC Biotechnology 13 43. (https://doi.org/10.1186/1472-6750-13-43)

    • Search Google Scholar
    • Export Citation
  • LapsiaVJohnsonRJDassBShimadaMKambhampatiGEjazNIArifAAEjazAA 2012 Elevated uric acid increases the risk for acute kidney injury. American Journal of Medicine 125 302.e9302.17. (https://doi.org/10.1016/j.amjmed.2011.06.021)

    • Search Google Scholar
    • Export Citation
  • MaiuoloJOppedisanoFGratteriSMuscoliCMollaceV 2016 Regulation of uric acid metabolism and excretion. International Journal of Cardiology 213 814. (https://doi.org/10.1016/j.ijcard.2015.08.109)

    • Search Google Scholar
    • Export Citation
  • MarincolaFCDessiAPattumelliMGCorbuSOssiciniCCiccarelliSAgostinoRMussapMFanosV 2015 1H NMR-based urine metabolic profile of IUGR, LGA, and AGA newborns in the first week of life. Clinica Chimica Acta 451 2834. (https://doi.org/10.1016/j.cca.2015.08.008)

    • Search Google Scholar
    • Export Citation
  • MussapMAntonucciRNotoAFanosV 2013 The role of metabolomics in neonatal and pediatric laboratory medicine. Clinica Chimica Acta 426 127138. (https://doi.org/10.1016/j.cca.2013.08.020)

    • Search Google Scholar
    • Export Citation
  • NeychevVKJinnahHA 2006 Sudden death in Lesch-Nyhan disease. Developmental Medicine and Child Neurology 48 923926. (https://doi.org/10.1017/S0012162206002015)

    • Search Google Scholar
    • Export Citation
  • NotoAFanosVDessiA 2016 Metabolomics in newborns. Advances in Clinical Chemistry 74 3561. (https://doi.org/10.1016/bs.acc.2015.12.006)

    • Search Google Scholar
    • Export Citation
  • OginoKKatoMFuruseYKinugasaYIshidaKOsakiSKinugawaTIgawaOHisatomeIShigemasaC 2010 Uric acid-lowering treatment with Benzbromarone in patients with heart failure: a double-blind placebo-controlled crossover preliminary study. Circulation Heart Failure 3 7381. (https://doi.org/10.1161/CIRCHEARTFAILURE.109.868604)

    • Search Google Scholar
    • Export Citation
  • ParkJMarjaniSLLaiLSamuelMWaxDDavisSRBrunoRSPratherRSYangXTianXC 2010 Altered gene expression profiles in the brain, kidney, and lung of deceased neonatal cloned pigs. Cellular Reprogramming 12 589597. (https://doi.org/10.1089/cell.2010.0004)

    • Search Google Scholar
    • Export Citation
  • ParkJYKimJHChoiYJHwangKCChoSKParkHHPaikSSKimTParkCLeeHT 2009 Comparative proteomic analysis of malformed umbilical cords from somatic cell nuclear transfer-derived piglets: implications for early postnatal death. BMC Genomics 10 511. (https://doi.org/10.1186/1471-2164-10-511)

    • Search Google Scholar
    • Export Citation
  • ParkMRChoSKLeeSYChoiYJParkJYKwonDNSonWJPaikSSKimTHanYMKimJH 2005 A rare and often unrecognized cerebromeningitis and hemodynamic disorder: a major cause of sudden death in somatic cell cloned piglets. Proteomics 5 19281939. (https://doi.org/10.1002/pmic.200401079)

    • Search Google Scholar
    • Export Citation
  • PerlsteinTSGumieniakOWilliamsGHSparrowDVokonasPSGazianoMWeissSTLitonjuaAA 2006 Uric acid and the development of hypertension: the normative aging study. Hypertension 48 10311036. (https://doi.org/10.1161/01.HYP.0000248752.08807.4c)

    • Search Google Scholar
    • Export Citation
  • PsychogiosNHauDDPengJGuoACMandalRBouatraSSinelnikovIKrishnamurthyREisnerRGautamB 2011 The human serum metabolome. PLoS ONE 6 e16957. (https://doi.org/10.1371/journal.pone.0016957)

    • Search Google Scholar
    • Export Citation
  • RichesPLWrightAFRalstonSH 2009 Recent insights into the pathogenesis of hyperuricaemia and gout. Human Molecular Genetics 18 R177R184. (https://doi.org/10.1093/hmg/ddp369)

    • Search Google Scholar
    • Export Citation
  • RiveraLSiddaiahROji-MmuoCSilveyraGRSilveyraP 2016 Biomarkers for bronchopulmonary dysplasia in the preterm infant. Frontiers in Pediatrics 4 33. (https://doi.org/10.3389/fped.2016.00033)

    • Search Google Scholar
    • Export Citation
  • RuanDPengJWangXOuyangZZouQYangYChenFGeWWuHLiuZ 2018 XIST derepression in active X chromosome hinders pig somatic cell nuclear transfer. Stem Cell Reports 10 494508. (https://doi.org/10.1016/j.stemcr.2017.12.015)

    • Search Google Scholar
    • Export Citation
  • RyuESKimMJShinHSJangYHChoiHSJoIJohnsonRJKangDH 2013 Uric acid-induced phenotypic transition of renal tubular cells as a novel mechanism of chronic kidney disease. American Journal of Physiology: Renal Physiology 304 F471F480. (https://doi.org/10.1152/ajprenal.00560.2012)

    • Search Google Scholar
    • Export Citation
  • SautinYYJohnsonRJ 2008 Uric acid: the oxidant-antioxidant paradox. Nucleosides Nucleotides and Nucleic Acids 27 608619. (https://doi.org/10.1080/15257770802138558)

    • Search Google Scholar
    • Export Citation
  • SchmidtMWintherKDSecherJOCallesenH 2015 Postmortem findings in cloned and transgenic piglets dead before weaning. Theriogenology 84 10141023. (https://doi.org/10.1016/j.theriogenology.2015.05.037)

    • Search Google Scholar
    • Export Citation
  • SiuYPLeungKTTongMKKwanTH 2006 Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. American Journal of Kidney Diseases 47 5159. (https://doi.org/10.1053/j.ajkd.2005.10.006)

    • Search Google Scholar
    • Export Citation
  • VernonHJ 2015 Inborn errors of metabolism advances in diagnosis and therapy. JAMA Pediatrics 169 778782. (https://doi.org/10.1001/jamapediatrics.2015.0754)

    • Search Google Scholar
    • Export Citation
  • XieBZhangHWeiRLiQWengXKongQLiuZ 2016 Histone H3 lysine 27 trimethylation acts as an epigenetic barrier in porcine nuclear reprogramming. Reproduction 151 916. (https://doi.org/10.1530/REP-15-0338)

    • Search Google Scholar
    • Export Citation
  • XuXHuJSongNChenRZhangTDingX 2017 Hyperuricemia increases the risk of acute kidney injury: a systematic review and meta-analysis. BMC Nephrology 18 27. (https://doi.org/10.1186/s12882-016-0433-1)

    • Search Google Scholar
    • Export Citation
  • YamanakaKSugimuraSWakaiTKawaharaMSatoE 2009 Acetylation level of histone H3 in early embryonic stages affects subsequent development of miniature pig somatic cell nuclear transfer embryos. Journal of Reproduction and Development 55 638644. (https://doi.org/10.1262/jrd.20245)

    • Search Google Scholar
    • Export Citation
  • YangHWuZ 2018 Genome editing of pigs for agriculture and biomedicine. Frontiers in Genetics 9 360. (https://doi.org/10.3389/fgene.2018.00360)

    • Search Google Scholar
    • Export Citation
  • YelkenBCaliskanYGorguluNAltunIYilmazAYaziciHOflazHYildizA 2012 Reduction of uric acid levels with allopurinol treatment improves endothelial function in patients with chronic kidney disease. Clinical Nephrology 77 275282. (https://doi.org/10.5414/cn107352)

    • Search Google Scholar
    • Export Citation
  • YiLShiSWangYHuangWXiaZAXingZPengWWangZ 2016 Serum metabolic profiling reveals altered metabolic pathways in patients with post-traumatic cognitive impairments. Scientific Reports 6 21320. (https://doi.org/10.1038/srep21320)

    • Search Google Scholar
    • Export Citation
  • ZhangASunHWangPHanYWangX 2012 Recent and potential developments of biofluid analyses in metabolomics. Journal of Proteomics 75 10791088. (https://doi.org/10.1016/j.jprot.2011.10.027)

    • Search Google Scholar
    • Export Citation
  • ZhouNCaoZWuRLiuXTaoJChenZSongDHanFLiYFangF 2014 Dynamic changes of histone H3 lysine 27 acetylation in pre-implantational pig embryos derived from somatic cell nuclear transfer. Animal Reproduction Science 148 153163. (https://doi.org/10.1016/j.anireprosci.2014.06.002)

    • Search Google Scholar
    • Export Citation
  • ZhouYFangLJiangLWenPCaoHHeWDaiCYangJ 2012 Uric acid induces renal inflammation via activating tubular NF-kappaB signaling pathway. PLoS ONE 7 e39738. (https://doi.org/10.1371/journal.pone.0039738)

    • Search Google Scholar
    • Export Citation