Hostname: page-component-586b7cd67f-t8hqh Total loading time: 0 Render date: 2024-11-26T08:45:13.309Z Has data issue: false hasContentIssue false
  • English
  • Français

Antenatal exposure to chorioamnionitis affects lipid metabolism in 7-week-old sheep

Published online by Cambridge University Press:  17 February 2012

E. Vlassaks ,
A. W. D. Gavilanes ,
V. Bieghs ,
A. Reinartz ,
N. Gassler ,
P. J. Van Gorp ,
M. J. J. Gijbels ,
O. Bekers ,
L. J. I. Zimmermann  and
J. J. Pillow
...Show all authors
E. Vlassaks
Affiliation:
Department of Pediatrics – Division of Neonatology, Maastricht University Medical Center, School of Mental Health and Neuroscience (MHeNS) and School for Oncology and Developmental Biology Maastricht (GROW), Maastricht, The Netherlands
A. W. D. Gavilanes
Affiliation:
Department of Pediatrics – Division of Neonatology, Maastricht University Medical Center, School of Mental Health and Neuroscience (MHeNS) and School for Oncology and Developmental Biology Maastricht (GROW), Maastricht, The Netherlands
V. Bieghs
Affiliation:
Department of Molecular Genetics and Pathology, Nutrition and Toxicology Research Institute (NUTRIM) and Cardiovascular Research Institute (CARIM) of Maastricht University, Maastricht, The Netherlands
A. Reinartz
Affiliation:
Department of Pathology, University Hospital Aachen, Aachen, Germany
N. Gassler
Affiliation:
Department of Pathology, University Hospital Aachen, Aachen, Germany
P. J. Van Gorp
Affiliation:
Department of Molecular Genetics and Pathology, Nutrition and Toxicology Research Institute (NUTRIM) and Cardiovascular Research Institute (CARIM) of Maastricht University, Maastricht, The Netherlands
M. J. J. Gijbels
Affiliation:
Department of Molecular Genetics and Pathology, Nutrition and Toxicology Research Institute (NUTRIM) and Cardiovascular Research Institute (CARIM) of Maastricht University, Maastricht, The Netherlands
O. Bekers
Affiliation:
Department of Clinical Chemistry, Maastricht University Medical Center, Maastricht, The Netherlands
L. J. I. Zimmermann
Affiliation:
Department of Pediatrics – Division of Neonatology, Maastricht University Medical Center, School of Mental Health and Neuroscience (MHeNS) and School for Oncology and Developmental Biology Maastricht (GROW), Maastricht, The Netherlands
J. J. Pillow
Affiliation:
School of Women's and Infants’ Health, University of Western Australia, Crawley, Western Australia
G. R. Polglase
Affiliation:
School of Women's and Infants’ Health, University of Western Australia, Crawley, Western Australia
I. Nitsos
Affiliation:
School of Women's and Infants’ Health, University of Western Australia, Crawley, Western Australia
J. P. Newnham
Affiliation:
School of Women's and Infants’ Health, University of Western Australia, Crawley, Western Australia
S. G. Kallapur
Affiliation:
Cincinnati Children's Hospital, Cincinnati, Ohio, USA
A. H. Jobe
Affiliation:
Cincinnati Children's Hospital, Cincinnati, Ohio, USA
R. Shiri-Sverdlov
Affiliation:
Department of Molecular Genetics and Pathology, Nutrition and Toxicology Research Institute (NUTRIM) and Cardiovascular Research Institute (CARIM) of Maastricht University, Maastricht, The Netherlands
B. W. Kramer*
Affiliation:
Department of Pediatrics – Division of Neonatology, Maastricht University Medical Center, School of Mental Health and Neuroscience (MHeNS) and School for Oncology and Developmental Biology Maastricht (GROW), Maastricht, The Netherlands
*
*Address for correspondence: Dr B. W. Kramer, MD, PhD, Professor of Experimental Perinatology, Department of Pediatrics, Maastricht University Medical Center, Postbus 5800, 6200MD Maastricht, The Netherlands. (Email b.kramer@mumc.nl)
Get access Rights & Permissions [Opens in a new window]

Abstract

Antenatal exposure of the fetus to inflammation may alter postnatal organ development. In our previous work, we demonstrated that the fetal liver is involved in the systemic inflammation associated with chorioamnionitis, leading to metabolic changes. On the basis of these findings, we hypothesized that chorioamnionitis can lead to postnatal inflammation-related liver injury and disturbed lipid metabolism. Chorioamnionitis was induced in sheep by intra-amniotic injection of lipopolysaccharide (LPS) or saline at 90, 100 and 110 days of gestation. Liver homeostasis and lipid metabolism were analyzed at term and at 7 weeks of age. At term, hepatic T-lymphocytes and apoptotic hepatocytes were increased. In addition, hepatic cholesterol and triglyceride levels were decreased in LPS-exposed animals compared with controls. At 7 weeks of age, no hepatic inflammation could be detected. However, liver triglycerides and plasma cholesterol levels were increased in LPS-exposed animals relative to controls. The changes in lipid levels at 7 weeks of age were associated with increased leptin receptor mRNA levels, increased lipid peroxidation, increased expression of cytochrome c oxidase subunit 4 as a marker for mitochondrial function and increased circulating ceramide levels. These findings demonstrate that chorioamnionitis-mediated antenatal inflammation-related liver disturbances have long-lasting postnatal effects on lipid metabolism.

Keywords

fetal origin of adult diseaselipopolysaccharideliver and lipid homeostasis
Type
Original Articles
Information
Journal of Developmental Origins of Health and Disease , Volume 3 , Issue 2 , April 2012 , pp. 103 - 110
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

†

Equal contribution of both authors.

References

1. Romero, R, Espinoza, J, Chaiworapongsa, T, Kalache, K. Infection and prematurity and the role of preventive strategies. Semin Neonatol. 2002; 7, 259–274.CrossRefGoogle ScholarPubMed
2. Goldenberg, RL, Hauth, JC, Andrews, WW. Intrauterine infection and preterm delivery. N Engl J Med. 2000; 342, 1500–1507.CrossRefGoogle ScholarPubMed
3. Gotsch, F, Romero, R, Kusanovic, JP, et al. . The fetal inflammatory response syndrome. Clin Obstet Gynecol. 2007; 50, 652–683.CrossRefGoogle ScholarPubMed
4. Gantert, M, Been, JV, Gavilanes, AW, et al. . Chorioamnionitis: a multiorgan disease of the fetus? J Perinatol. 2010; 30 (Suppl), S21–S30.CrossRefGoogle ScholarPubMed
5. Romero, R, Espinoza, J, Goncalves, LF, et al. . The role of inflammation and infection in preterm birth. Semin Reprod Med. 2007; 25, 21–39.CrossRefGoogle Scholar
6. Been, JV, Zimmermann, LJ. Histological chorioamnionitis and respiratory outcome in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2009; 94, F218–F225.CrossRefGoogle ScholarPubMed
7. Wouters, K, van Gorp, PJ, Bieghs, V, et al. . Dietary cholesterol, rather than liver steatosis, leads to hepatic inflammation in hyperlipidemic mouse models of nonalcoholic steatohepatitis. Hepatology. 2008; 48, 474–486.CrossRefGoogle ScholarPubMed
8. Bieghs, V, Vlassaks, E, Custers, A, et al. . Chorioamnionitis induced hepatic inflammation and disturbed lipid metabolism in fetal sheep. Pediatr Res. 2010; 68, 466–472.CrossRefGoogle ScholarPubMed
9. Roseboom, TJ, van der Meulen, JH, Ravelli, AC, et al. . Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview. Mol Cell Endocrinol. 2001; 185, 93–98.CrossRefGoogle Scholar
10. Kramer, BW, Moss, TJ, Willet, KE, et al. . Dose and time response after intraamniotic endotoxin in preterm lambs. Am J Respir Crit Care Med. 2001; 164, 982–988.CrossRefGoogle ScholarPubMed
11. Kramer, BW, Kaemmerer, U, Kapp, M, et al. . Decreased expression of angiogenic factors in placentas with chorioamnionitis after preterm birth. Pediatr Res. 2005; 58, 607–612.CrossRefGoogle ScholarPubMed
12. Kramer, BW, Ikegami, M, Jobe, AH. Intratracheal endotoxin causes systemic inflammation in ventilated preterm lambs. Am J Respir Crit Care Med. 2002; 165, 463–469.CrossRefGoogle ScholarPubMed
13. Kramer, BW, Jobe, AH. The clever fetus: responding to inflammation to minimize lung injury. Biol Neonate. 2005; 88, 202–207.CrossRefGoogle ScholarPubMed
14. Kramer, BW, Kramer, S, Ikegami, M, Jobe, AH. Injury, inflammation, and remodeling in fetal sheep lung after intra-amniotic endotoxin. Am J Physiol Lung Cell Mol Physiol. 2002; 283, L452–L459.CrossRefGoogle ScholarPubMed
15. Kallapur, SG, Willet, KE, Jobe, AH, Ikegami, M, Bachurski, CJ. Intra-amniotic endotoxin: chorioamnionitis precedes lung maturation in preterm lambs. Am J Physiol Lung Cell Mol Physiol. 2001; 280, L527–L536.CrossRefGoogle ScholarPubMed
16. Newnham, JP, Kallapur, SG, Kramer, BW, et al. . Betamethasone effects on chorioamnionitis induced by intra-amniotic endotoxin in sheep. Am J Obstet Gynecol. 2003; 189, 1458–1466.CrossRefGoogle ScholarPubMed
17. Lee, AJ, Lambermont, VA, Pillow, JJ, et al. . Fetal responses to lipopolysaccharide-induced chorioamnionitis alter immune and airway responses in 7-week-old sheep. Am J Obstet Gynecol. 2011; 204, 364.e17–364.e24.CrossRefGoogle ScholarPubMed
18. Shiri-Sverdlov, R, Wouters, K, van Gorp, PJ, et al. . Early diet-induced non-alcoholic steatohepatitis in APOE2 knock-in mice and its prevention by fibrates. J Hepatol. 2006; 44, 732–741.CrossRefGoogle ScholarPubMed
19. Shaner, RL, Allegood, JC, Park, H, et al. . Quantitative analysis of sphingolipids for lipidomics using triple quadrupole and quadrupole linear ion trap mass spectrometers. J Lipid Res. 2009; 50, 1692–1707.CrossRefGoogle ScholarPubMed
20. Yang, G, Badeanlou, L, Bielawski, J, et al. . Central role of ceramide biosynthesis in body weight regulation, energy metabolism, and the metabolic syndrome. Am J Physiol Endocrinol Metab. 2009; 297, E211–E224.CrossRefGoogle ScholarPubMed
21. Alkhouri, N, Dixon, LJ, Feldstein, AE. Lipotoxicity in nonalcoholic fatty liver disease: not all lipids are created equal. Expert Rev Gastroenterol Hepatol. 2009; 3, 445–451.CrossRefGoogle Scholar
22. Pejznochova, M, Tesarova, M, Hansikova, H, et al. . Mitochondrial DNA content and expression of genes involved in mtDNA transcription, regulation and maintenance during human fetal development. Mitochondrion. 10, 321–329.CrossRefGoogle Scholar
23. Wei, Y, Clark, SE, Thyfault, JP, et al. . Oxidative stress-mediated mitochondrial dysfunction contributes to angiotensin II-induced nonalcoholic fatty liver disease in transgenic Ren2 rats. Am J Pathol. 2009; 174, 1329–1337.CrossRefGoogle ScholarPubMed
24. Jobe, AH, Ikegami, M. Antenatal infection/inflammation and postnatal lung maturation and injury. Respir Res. 2001; 2, 27–32.CrossRefGoogle ScholarPubMed
25. Normann, E, Lacaze-Masmonteil, T, Eaton, F, et al. . A novel mouse model of Ureaplasma-induced perinatal inflammation: effects on lung and brain injury. Pediatr Res. 2009; 65, 430–436.CrossRefGoogle ScholarPubMed
26. Yoder, BA, Coalson, JJ, Winter, VT, et al. . Effects of antenatal colonization with ureaplasma urealyticum on pulmonary disease in the immature baboon. Pediatr Res. 2003; 54, 797–807.CrossRefGoogle ScholarPubMed
27. Godfrey, KM, Gluckman, PD, Hanson, MA. Developmental origins of metabolic disease: life course and intergenerational perspectives. Trends Endocrinol Metab. 2010; 21, 199–205.CrossRefGoogle ScholarPubMed
28. Caille, V, Bossi, P, Grimaldi, D, Vieillard-Baro, A. Physiopathology of severe sepsis. Presse Med. 2004; 33, 256–261, discussion 269.CrossRefGoogle ScholarPubMed
29. Loria, V, Dato, I, Graziani, F, Biasucci, LM. Myeloperoxidase: a new biomarker of inflammation in ischemic heart disease and acute coronary syndromes. Mediators Inflamm. 2008; 2008, 135625.CrossRefGoogle Scholar
30. Wolfs, TG, Buurman, WA, Zoer, B, et al. . Endotoxin induced chorioamnionitis prevents intestinal development during gestation in fetal sheep. PLoS One. 2009; 4, e5837.CrossRefGoogle ScholarPubMed
31. Schwarzenberg, SJ, Potter, CJ, Berry, SA. Developmental regulation of the hepatic acute phase response. Am J Physiol. 1991; 261, C461–C466.CrossRefGoogle ScholarPubMed
32. Patricolo, M, Zangari, A, Paolocci, N, et al. . In utero partial liver resection in the rabbit model: a study on fetal tissue regeneration. Fetal Diagn Ther. 1997; 12, 232–235.CrossRefGoogle Scholar
33. Mundt, B, Wirth, T, Zender, L, et al. . Tumour necrosis factor related apoptosis inducing ligand (TRAIL) induces hepatic steatosis in viral hepatitis and after alcohol intake. Gut. 2005; 54, 1590–1596.CrossRefGoogle ScholarPubMed
34. Chikano, S, Sawada, K, Shimoyama, T, et al. . IL-18 and IL-12 induce intestinal inflammation and fatty liver in mice in an IFN-gamma dependent manner. Gut. 2000; 47, 779–786.CrossRefGoogle Scholar
35. Duffield, JA, Vuocolo, T, Tellam, R, et al. . Placental restriction of fetal growth decreases IGF1 and leptin mRNA expression in the perirenal adipose tissue of late gestation fetal sheep. Am J Physiol Regul Integr Comp Physiol. 2008; 294, R1413–R1419.CrossRefGoogle ScholarPubMed
36. Demeilliers, C, Maisonneuve, C, Grodet, A, et al. . Impaired adaptive resynthesis and prolonged depletion of hepatic mitochondrial DNA after repeated alcohol binges in mice. Gastroenterology. 2002; 123, 1278–1290.CrossRefGoogle ScholarPubMed
37. Memon, RA, Holleran, WM, Moser, AH, et al. . Endotoxin and cytokines increase hepatic sphingolipid biosynthesis and produce lipoproteins enriched in ceramides and sphingomyelin. Arterioscler Thromb Vasc Biol. 1998; 18, 1257–1265.CrossRefGoogle ScholarPubMed
38. Zimmermann, C, Ginis, I, Furuya, K, et al. . Lipopolysaccharide-induced ischemic tolerance is associated with increased levels of ceramide in brain and in plasma. Brain Res. 2001; 895, 59–65.CrossRefGoogle ScholarPubMed
39. Ruvolo, PP. Intracellular signal transduction pathways activated by ceramide and its metabolites. Pharmacol Res. 2003; 47, 383–392.CrossRefGoogle ScholarPubMed
40. Browning, JD, Horton, JD. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest. 2004; 114, 147–152.CrossRefGoogle ScholarPubMed
Supplementary material: Image

Vlassaks supplementary material

Vlassaks supplementary material

Download Vlassaks supplementary material(Image)
Image 93 KB