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Novel thromboxane A2 analog-induced IUGR mouse model

Published online by Cambridge University Press:  13 September 2011

C. Fung*
Affiliation:
Pediatrics/Neonatology, University of Utah, Salt Lake City, UT, USA
A. Brown
Affiliation:
Pediatrics/Neonatology, University of Utah, Salt Lake City, UT, USA
J. Cox
Affiliation:
Pediatrics/Neonatology, University of Utah, Salt Lake City, UT, USA
C. Callaway
Affiliation:
Pediatrics/Neonatology, University of Utah, Salt Lake City, UT, USA
R. McKnight
Affiliation:
Pediatrics/Neonatology, University of Utah, Salt Lake City, UT, USA
R. Lane
Affiliation:
Pediatrics/Neonatology, University of Utah, Salt Lake City, UT, USA
*
*Address for correspondence: Dr C. Fung, Pediatrics/Neonatology, University of Utah, Salt Lake City, UT, USA. (Email camille.fung@hsc.utah.edu)

Abstract

Rodents, particularly rats, are used in the majority of intrauterine growth restriction (IUGR) research. An important tool that is lacking in this field is the ability to impose IUGR on transgenic mice. We therefore developed a novel mouse model of chronic IUGR using U-46619, a thromboxane A2 (TXA2) analog, infusion. TXA2 overproduction is prevalent in human pregnancies complicated by cigarette smoking, diabetes mellitus and preeclampsia. In this model, U-46619 micro-osmotic pump infusion in the last week of C57BL/6J mouse gestation caused maternal hypertension. IUGR pups weighed 15% less, had lighter brain, lung, liver and kidney weights, but had similar nose-to-anus lengths compared with sham pups at birth. Metabolically, IUGR pups showed increased essential branched-chain amino acids. They were normoglycemic yet hypoinsulinemic. They showed decreased hepatic mRNA levels of total insulin-like growth factor-1 and its variants, but increased level of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha. IUGR offspring were growth restricted from birth (P1) through postnatal day 21 (P21). IUGR males caught up with sham males in weight by P28, whereas IUGR females caught up with sham females by P77. IUGR males surpassed sham males in weight by P238. In summary, we have a non-brain sparing IUGR mouse model that has a relative ease of surgical IUGR induction and exhibits features similar to the chronic IUGR offspring of humans and other animal models. As transgenic technology predominates in mice, this model now permits the imposition of IUGR on transgenic mice to interrogate mechanisms of fetal origins of adult disease.

Type
Original Articles
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2011

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References

1.Schroder, HJ. Models of fetal growth restriction. Eur J Obstet Gynecol Reprod Biol. 2003; 110(Suppl. 1), S29S39.CrossRefGoogle ScholarPubMed
2.Battaglia, FC, Lubchenco, LO. A practical classification of newborn infants by weight and gestational age. J Pediatr. 1967; 71, 159163.CrossRefGoogle ScholarPubMed
3.Barker, DJ. The origins of the developmental origins theory. J Intern Med. 2007; 261, 412417.CrossRefGoogle ScholarPubMed
4.Vuguin, PM. Animal models for small for gestational age and fetal programming of adult disease. Horm Res. 2007; 68, 113123.Google ScholarPubMed
5.Wigglesworth, JS. Experimental growth retardation in the foetal rat. J Pathol Bacteriol. 1964; 88, 113.CrossRefGoogle ScholarPubMed
6.Ogata, ES, Bussey, ME, LaBarbera, A, Finley, S. Altered growth, hypoglycemia, hypoalaninemia, and ketonemia in the young rat: postnatal consequences of intrauterine growth retardation. Pediatr Res. 1985; 19, 3237.CrossRefGoogle Scholar
7.Lane, RH, Flozak, AS, Ogata, ES, Bell, GI, Simmons, RA. Altered hepatic gene expression of enzymes involved in energy metabolism in the growth-retarded fetal rat. Pediatr Res. 1996; 39, 390394.CrossRefGoogle ScholarPubMed
8.Lane, RH, Ramirez, RJ, Tsirka, AE, et al. Uteroplacental insufficiency lowers the threshold towards hypoxia-induced cerebral apoptosis in growth-retarded fetal rats. Brain Res. 2001; 895, 186193.CrossRefGoogle ScholarPubMed
9.McAdam, BF, Byrne, D, Morrow, JD, Oates, JA. Contribution of cyclooxygenase-2 to elevated biosynthesis of thromboxane A2 and prostacyclin in cigarette smokers. Circulation. 2005; 112, 10241029.CrossRefGoogle ScholarPubMed
10.Goodwill, AG, James, ME, Frisbee, JC. Increased vascular thromboxane generation impairs dilation of skeletal muscle arterioles of obese Zucker rats with reduced oxygen tension. Am J Physiol Heart Circ Physiol. 2008; 295, H1522H1528.CrossRefGoogle ScholarPubMed
11.Tanbe, AF, Khalil, RA. Circulating and vascular bioactive factors during hypertension in pregnancy. Curr Bioact Compd. 2010; 6, 6075.CrossRefGoogle ScholarPubMed
12.Rocca, B, Loeb, AL, Strauss, JF III, et al. Directed vascular expression of the thromboxane A2 receptor results in intrauterine growth retardation. Nat Med. 2000; 6, 219221.CrossRefGoogle ScholarPubMed
13.Hayakawa, M, Takemoto, K, Nakayama, A, et al. An animal model of intrauterine growth retardation induced by synthetic thromboxane a(2). J Soc Gynecol Investig. 2006; 13, 566572.CrossRefGoogle ScholarPubMed
14.Ogata, ES, Bussey, ME, Finley, S. Altered gas exchange, limited glucose and branched chain amino acids, and hypoinsulinism retard fetal growth in the rat. Metabolism. 1986; 35, 970977.CrossRefGoogle ScholarPubMed
15.Gentili, S, Morrison, JL, McMillen, IC. Intrauterine growth restriction and differential patterns of hepatic growth and expression of IGF1, PCK2, and HSDL1 mRNA in the sheep fetus in late gestation. Biol Reprod. 2009; 80, 11211127.CrossRefGoogle ScholarPubMed
16.Randhawa, RS. The insulin-like growth factor system and fetal growth restriction. Pediatr Endocrinol Rev. 2008; 6, 235240.Google Scholar
17.Lane, RH, MacLennan, NK, Hsu, JL, Janke, SM, Pham, TD. Increased hepatic peroxisome proliferator-activated receptor-gamma coactivator-1 gene expression in a rat model of intrauterine growth retardation and subsequent insulin resistance. Endocrinology. 2002; 143, 24862490.CrossRefGoogle Scholar
18.Adamo, ML, Neuenschwander, S, LeRoith, D, Roberts, CT Jr. Structure, expression, and regulation of the IGF-I gene. Adv Exp Med Biol. 1993; 343, 111.Google ScholarPubMed
19.Beale, EG, Hammer, RE, Antoine, B, Forest, C. Disregulated glyceroneogenesis: PCK1 as a candidate diabetes and obesity gene. Trends Endocrinol Metab. 2004; 15, 129135.CrossRefGoogle ScholarPubMed
20.Meirhaeghe, A, Crowley, V, Lenaghan, C, et al. Characterization of the human, mouse and rat PGC1 beta (peroxisome-proliferator-activated receptor-gamma co-activator 1 beta) gene in vitro and in vivo. Biochem J. 2003; 373, 155165.CrossRefGoogle ScholarPubMed
21.Krege, JH, Hodgin, JB, Hagaman, JR, Smithies, O. A noninvasive computerized tail-cuff system for measuring blood pressure in mice. Hypertension. 1995; 25, 11111115.CrossRefGoogle ScholarPubMed
22.Roberts, LJ II, Sweetman, BJ, Oates, JA. Metabolism of thromboxane B2 in man. Identification of twenty urinary metabolites. J Biol Chem. 1981; 256, 83848393.CrossRefGoogle ScholarPubMed
23.Pradelles, P, Grassi, J, Maclouf, J. Enzyme immunoassays of eicosanoids using acetylcholine esterase as label: an alternative to radioimmunoassay. Anal Chem. 1985; 57, 11701173.CrossRefGoogle ScholarPubMed
24.A, J, Trygg, J, Gullberg, J, et al. Extraction and GC/MS analysis of the human blood plasma metabolome. Anal Chem. 2005; 77, 80868094.CrossRefGoogle ScholarPubMed
25.MacLennan, NK, James, SJ, Melnyk, S, et al. Uteroplacental insufficiency alters DNA methylation, one-carbon metabolism, and histone acetylation in IUGR rats. Physiol Genomics. 2004; 18, 4350.CrossRefGoogle ScholarPubMed
26.Pham, TD, MacLennan, NK, Chiu, CT, et al. Uteroplacental insufficiency increases apoptosis and alters p53 gene methylation in the full-term IUGR rat kidney. Am J Physiol Regul Integr Comp Physiol. 2003; 285, R962R970.CrossRefGoogle ScholarPubMed
27.van Nas, A, Guhathakurta, D, Wang, SS, et al. Elucidating the role of gonadal hormones in sexually dimorphic gene coexpression networks. Endocrinology. 2009; 150, 12351249.CrossRefGoogle ScholarPubMed
28.Smirnov, AN. Hormonal mechanisms of sex differentiation of the liver: the modern concepts and problems. Ontogenez. 2009; 40, 334354.Google Scholar
29.Joss-Moore, LA, Wang, Y, Campbell, MS, et al. Uteroplacental insufficiency increases visceral adiposity and visceral adipose PPARgamma2 expression in male rat offspring prior to the onset of obesity. Early Hum Dev. 2010; 86, 179185.CrossRefGoogle Scholar
30.Baserga, M, Hale, MA, Wang, ZM, et al. Uteroplacental insufficiency alters nephrogenesis and downregulates cyclooxygenase-2 expression in a model of IUGR with adult-onset hypertension. Am J Physiol Regul Integr Comp Physiol. 2007; 292, R1943R1955.CrossRefGoogle Scholar
31.Eskenazi, B, Fenster, L, Sidney, S, Elkin, EP. Fetal growth retardation in infants of multiparous and nulliparous women with preeclampsia. Am J Obstet Gynecol. 1993; 169, 11121118.CrossRefGoogle ScholarPubMed
32.Pietrantoni, M, O'Brien, WF. The current impact of the hypertensive disorders of pregnancy. Clin Exp Hypertens. 1994; 16, 479492.CrossRefGoogle ScholarPubMed
33.Duncan, JR, Cock, ML, Loeliger, M, et al. Effects of exposure to chronic placental insufficiency on the postnatal brain and retina in sheep. J Neuropathol Exp Neurol. 2004; 63, 11311143.CrossRefGoogle ScholarPubMed
34.Li, RY, Tsutsui, Y. Growth retardation and microcephaly induced in mice by placental infection with murine cytomegalovirus. Teratology. 2000; 62, 7985.3.0.CO;2-S>CrossRefGoogle ScholarPubMed
35.von Versen-Hoeynck, FM, Powers, RW. Maternal-fetal metabolism in normal pregnancy and preeclampsia. Front Biosci. 2007; 12, 24572470.CrossRefGoogle ScholarPubMed
36.Evans, RW, Powers, RW, Ness, RB, et al. Maternal and fetal amino acid concentrations and fetal outcomes during pre-eclampsia. Reproduction. 2003; 125, 785790.CrossRefGoogle ScholarPubMed
37.Barry, JS, Rozance, PJ, Anthony, RV. An animal model of placental insufficiency-induced intrauterine growth restriction. Semin Perinatol. 2008; 32, 225230.CrossRefGoogle ScholarPubMed
38.Foley, TP Jr, DePhilip, R, Perricelli, A, Miller, A. Low somatomedin activity in cord serum from infants with intrauterine growth retardation. J Pediatr. 1980; 96, 605610.CrossRefGoogle ScholarPubMed
39.Unterman, TG, Simmons, RA, Glick, RP, Ogata, ES. Circulating levels of insulin, insulin-like growth factor-I (IGF-I), IGF-II, and IGF-binding proteins in the small for gestational age fetal rat. Endocrinology. 1993; 132, 327336.CrossRefGoogle ScholarPubMed
40.Baker, J, Liu, JP, Robertson, EJ, Efstratiadis, A. Role of insulin-like growth factors in embryonic and postnatal growth. Cell. 1993; 75, 7382.CrossRefGoogle ScholarPubMed
41.Fu, Q, Yu, X, Callaway, CW, Lane, RH, McKnight, RA. Epigenetics: intrauterine growth retardation (IUGR) modifies the histone code along the rat hepatic IGF-1 gene. FASEB J. 2009; 23, 24382449.CrossRefGoogle ScholarPubMed
42.Varvarigou, AA. Intrauterine growth restriction as a potential risk factor for disease onset in adulthood. J Pediatr Endocrinol Metab. 2010; 23, 215224.CrossRefGoogle ScholarPubMed
43.Veening, MA, Van Weissenbruch, MM, Delemarre-Van De Waal, HA. Glucose tolerance, insulin sensitivity, and insulin secretion in children born small for gestational age. J Clin Endocrinol Metab. 2002; 87, 46574661.CrossRefGoogle ScholarPubMed
44.Barker, DJ, Eriksson, JG, Forsen, T, Osmond, C. Fetal origins of adult disease: strength of effects and biological basis. Int J Epidemiol. 2002; 31, 12351239.CrossRefGoogle ScholarPubMed
45.Hensen, K, Braem, C, Declercq, J, et al. Targeted disruption of the murine Plag1 proto-oncogene causes growth retardation and reduced fertility. Dev Growth Differ. 2004; 46, 459470.CrossRefGoogle ScholarPubMed
46.Tamemoto, H, Kadowaki, T, Tobe, K, et al. Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1. Nature. 1994; 372, 182186.CrossRefGoogle ScholarPubMed
47.Vuguin, PM, Kedees, MH, Cui, L, et al. Ablation of the glucagon receptor gene increases fetal lethality and produces alterations in islet development and maturation. Endocrinology. 2006; 147, 39954006.CrossRefGoogle ScholarPubMed
48.Collins, LL, Lee, YF, Heinlein, CA, et al. Growth retardation and abnormal maternal behavior in mice lacking testicular orphan nuclear receptor 4. Proc Natl Acad Sci U S A. 2004; 101, 1505815063.CrossRefGoogle ScholarPubMed
49.Hansen, TV, Hammer, NA, Nielsen, J, et al. Dwarfism and impaired gut development in insulin-like growth factor II mRNA-binding protein 1-deficient mice. Mol Cell Biol. 2004; 24, 44484464.CrossRefGoogle ScholarPubMed
50.Crossey, PA, Pillai, CC, Miell, JP. Altered placental development and intrauterine growth restriction in IGF binding protein-1 transgenic mice. J Clin Invest. 2002; 110, 411418.CrossRefGoogle ScholarPubMed
51.Li, M, Yee, D, Magnuson, TR, Smithies, O, Caron, KM. Reduced maternal expression of adrenomedullin disrupts fertility, placentation, and fetal growth in mice. J Clin Invest. 2006; 116, 26532662.CrossRefGoogle ScholarPubMed
52.Ivanova, M, Dobrzycka, KM, Jiang, S, et al. Scaffold attachment factor B1 functions in development, growth, and reproduction. Mol Cell Biol. 2005; 25, 29953006.CrossRefGoogle ScholarPubMed
53.Yoshida, T, Gan, Q, Franke, AS, et al. Smooth and cardiac muscle-selective knockout of Kruppel-like factor 4 causes postnatal death and growth retardation. J Biol Chem. 2010; 285, 2117521184.CrossRefGoogle ScholarPubMed
54.Esposito, ER, Horn, KH, Greene, RM, Pisano, MM. An animal model of cigarette smoke-induced in utero growth retardation. Toxicology. 2008; 246, 193202.CrossRefGoogle ScholarPubMed
55.Gandley, RE, Jeyabalan, A, Desai, K, et al. Cigarette exposure induces changes in maternal vascular function in a pregnant mouse model. Am J Physiol Regul Integr Comp Physiol. 2010; 298, R1249R1256.CrossRefGoogle Scholar
56.Kaminen-Ahola, N, Ahola, A, Maga, M, et al. Maternal ethanol consumption alters the epigenotype and the phenotype of offspring in a mouse model. PLoS Genet. 2010; 6, e1000811.CrossRefGoogle ScholarPubMed
57.Coe, BL, Kirkpatrick, JR, Taylor, JA, vom Saal, FS. A new ‘crowded uterine horn’ mouse model for examining the relationship between foetal growth and adult obesity. Basic Clin Pharmacol Toxicol. 2008; 102, 162167.CrossRefGoogle ScholarPubMed
58.Sutton, GM, Centanni, AV, Butler, AA. Protein malnutrition during pregnancy in C57BL/6J mice results in offspring with altered circadian physiology before obesity. Endocrinology. 2010; 151, 15701580.CrossRefGoogle ScholarPubMed
59.Bobetsis, YA, Barros, SP, Lin, DM, Arce, RM, Offenbacher, S. Altered gene expression in murine placentas in an infection-induced intrauterine growth restriction model: a microarray analysis. J Reprod Immunol. 2010; 85, 140148.CrossRefGoogle Scholar