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The impact of maternal protein restriction during perinatal life on the response to a septic insult in adult rats

Published online by Cambridge University Press:  23 December 2020

Reza Khazaee
Affiliation:
Biotron Research Centre, London, Ontario, Canada
Anastasiya Vinokurtseva
Affiliation:
Department of Pathology and Laboratory Medicine, The University of Western Ontario, London, Ontario, Canada
Lynda A. McCaig
Affiliation:
Lawson Health Research Institute, London, Ontario, Canada
Cory Yamashita
Affiliation:
Department of Physiology & Pharmacology, The University of Western Ontario, London, Ontario, Canada Department of Medicine, The University of Western Ontario, London, Ontario, Canada Lawson Health Research Institute, London, Ontario, Canada
Daniel B. Hardy
Affiliation:
Department of Physiology & Pharmacology, The University of Western Ontario, London, Ontario, Canada Department of Obstetrics & Gynecology, The University of Western Ontario, London, Ontario, Canada Lawson Health Research Institute, London, Ontario, Canada
Edith Arany
Affiliation:
Department of Pathology and Laboratory Medicine, The University of Western Ontario, London, Ontario, Canada Lawson Health Research Institute, London, Ontario, Canada
Ruud A. W. Veldhuizen*
Affiliation:
Department of Physiology & Pharmacology, The University of Western Ontario, London, Ontario, Canada Department of Obstetrics & Gynecology, The University of Western Ontario, London, Ontario, Canada Lawson Health Research Institute, London, Ontario, Canada
*
*Address for correspondence: Ruud Veldhuizen, Lawson Health Research Institute, E4-110268 Grosvenor St., London, ON, N6A 4V2, Canada. Email: [email protected]

Abstract

Although abundant evidence exists that adverse events during pregnancy lead to chronic conditions, there is limited information on the impact of acute insults such as sepsis. This study tested the hypothesis that impaired fetal development leads to altered organ responses to a septic insult in both male and female adult offspring. Fetal growth restricted (FGR) rats were generated using a maternal protein-restricted diet. Male and female FGR and control diet rats were housed until 150–160 d of age when they were exposed either a saline (control) or a fecal slurry intraperitoneal (Sepsis) injection. After 6 h, livers and lungs were analyzed for inflammation and, additionally, the amounts and function of pulmonary surfactant were measured. The results showed increases in the steady-state mRNA levels of inflammatory cytokines in the liver in response to the septic insult in both males and females; these responses were not different between FGR and control diet groups. In the lungs, cytokines were not detectable in any of the experimental groups. A significant decrease in the relative amount of surfactant was observed in male FGR offspring, but this was not observed in control males or in female animals. Overall, it is concluded that FGR induced by maternal protein restriction does not impact liver and lung inflammatory response to sepsis in either male or female adult rats. An altered septic response in male FGR offspring with respect to surfactant may imply a contribution to lung dysfunction.

Type
Original Article
Copyright
© The Author(s), 2020. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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Footnotes

*

Authors made equal contributions to this manuscript.

References

El Hajj, N, Schneider, E, Lehnen, H, Haaf, T. Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment. Reproduction. 2014; 148(6), R111R120.10.1530/REP-14-0334CrossRefGoogle ScholarPubMed
Harding, R, Maritz, G. Maternal and fetal origins of lung disease in adulthood. Semin Fetal Neonatal Med. 2012; 17, 6772.10.1016/j.siny.2012.01.005CrossRefGoogle ScholarPubMed
Pike, K, Jane Pillow, J, Lucas, JS. Long term respiratory consequences of intrauterine growth restriction. Semin Fetal Neonatal Med. 2012; 17(2), 9298.10.1016/j.siny.2012.01.003CrossRefGoogle ScholarPubMed
Dasinger, JH, Alexander, BT. Gender differences in developmental programming of cardiovascular diseases. Clin Sci (Lond). 2016; 130(5), 337348.10.1042/CS20150611CrossRefGoogle ScholarPubMed
Sohi, G, Revesz, A, Hardy, DB. Nutritional mismatch in postnatal life of low birth weight rat offspring leads to increased phosphorylation of hepatic eukaryotic initiation factor 2 α in adulthood. Metabolism. 2013; 62(10), 13671374.10.1016/j.metabol.2013.05.002CrossRefGoogle ScholarPubMed
Chamson-Reig, A, Thyssen, SM, Hill, DJ, Arany, E. Exposure of the pregnant rat to low protein diet causes impaired glucose homeostasis in the young adult offspring by different mechanisms in males and females. Exp Biol Med. 2009; 234(12), 14251436.10.3181/0902-RM-69CrossRefGoogle Scholar
Sohi, G, Revesz, A, Ramkumar, J, Hardy, DB. Higher hepatic MIR-29 expression in undernourished male rats during the postnatal period targets the long-term repression of IGF-1. Endocrinology. 2015; 156(9), 30693076.Google ScholarPubMed
Sundrani, DP, Roy, SS, Jadhav, AT, Joshi, SR. Sex-specific differences and developmental programming for diseases in later life. Reprod Fertil Dev. 2017; 29(11), 20852099.10.1071/RD16265CrossRefGoogle ScholarPubMed
Chen, T, Liu, H, Yan, H, Wu, D, Ping, J. Developmental origins of inflammatory and immune diseases. Mol Hum Reprod. 2016; 22(8), 558565.CrossRefGoogle ScholarPubMed
Husak, L, Marcuzzi, A, Herring, J, et al. National analysis of sepsis hospitalizations and factors contributing to sepsis in-hospital mortality in Canada. Health Q. 2010; 13, 3541.10.12927/hcq.2010.21963CrossRefGoogle ScholarPubMed
Angus, DC, Linde-Zwirble, WT, Lidicker, J, Clermont, G, Carcillo, J, Pinsky, MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001; 29(7), 13031310.10.1097/00003246-200107000-00002CrossRefGoogle ScholarPubMed
Singer, M, Bellomo, R, Bernard, GR, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). Jama. 2016; 315(8), 801810.10.1001/jama.2016.0287CrossRefGoogle Scholar
Bauer, M, Press, AT, Trauner, M. The liver in sepsis: patterns of response and injury. Curr Opin Crit Care. 2013; 19(2), 123127.10.1097/MCC.0b013e32835eba6dCrossRefGoogle ScholarPubMed
Happel, KI, Nelson, S, Summer, W. The lung in sepsis: fueling the fire. Am J Med Sci. 2004; 328(4), 230237.10.1097/00000441-200410000-00006CrossRefGoogle Scholar
Malloy, J, McCaig, L, Veldhuizen, R, et al. Alterations of the endogenous surfactant system in septic adult rats. Am J Resp Crit Care Med. 1997; 156, 617623.10.1164/ajrccm.156.2.9608009CrossRefGoogle ScholarPubMed
Yan, J, Song, L, Shulin, L. The role of the liver in sepsis. Int Rev Immunol. 2014; 33(6), 498510.10.3109/08830185.2014.889129CrossRefGoogle ScholarPubMed
Sohi, G, Marchand, K, Revesz, A, Arany, E, Hardy, DB. Maternal protein restriction elevates cholesterol in adult rat offspring due to repressive changes in histone modifications at the cholesterol 7α -hydroxylase promoter. Mol Endocrinol. 2011; 25(5), 785798.CrossRefGoogle ScholarPubMed
Khazaee, R, Mccaig, LA, Yamashita, C, Hardy, DB, Veldhuizen, RAW. Maternal protein restriction during perinatal life affects lung mechanics and the surfactant system during early postnatal life in female rats. PLoS One. 2019; 14(4), 113.10.1371/journal.pone.0215611CrossRefGoogle ScholarPubMed
Tyml, K, Swarbreck, S, Pape, C, et al. Voluntary running exercise protects against sepsis-induced early inflammatory and pro-coagulant responses in aged mice. Crit Care. 2017; 21(1), 210.10.1186/s13054-017-1783-1CrossRefGoogle ScholarPubMed
Shrum, B, Anantha, R V., Xu, SX, et al. A robust scoring system to evaluate sepsis severity in an animal model. BMC Res Notes. 2014; 7(1), 111.10.1186/1756-0500-7-233CrossRefGoogle ScholarPubMed
Vandesompele, J, De Preter, K, Pattyn, F, et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002; 3(7), 7.10.1186/gb-2002-3-7-research0034CrossRefGoogle ScholarPubMed
Pfaffl, MW, Tichopad, A, Prgomet, C, Neuvians, TP. Determination of stable housekeeping genes, differentially regulated target genes and sample integrity: bestkeeper - excel-based tool using pair-wise correlations. Biotechnol Lett. 2004; 26(6), 509515.10.1023/B:BILE.0000019559.84305.47CrossRefGoogle ScholarPubMed
Maruscak, AA, Vockeroth, DW, Girardi, B, et al. Alterations to surfactant precede physiological deterioration during high tidal volume ventilation. Am J Physiol Lung Cell Mol Physiol. 2008; 294(5), L974L983.CrossRefGoogle ScholarPubMed
Duck-Chong, CG. A rapid sensitive method for determining phospholipid phosphorus involving digestion with magnesium nitrate. Lipids. 1979; 14, 492497.CrossRefGoogle Scholar
Bligh, EG, Dyer, WJ. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959; 37, 911917.10.1139/y59-099CrossRefGoogle ScholarPubMed
Goerke, J. Pulmonary surfactant: functions and molecular composition. Biochim Biophys Acta. 1998; 1408(2–3), 7989.CrossRefGoogle ScholarPubMed
Lewis, JF, Veldhuizen, R, Possmayer, F, et al. Altered alveolar surfactant is an early marker of acute lung injury in septic adult sheep. Am J Respir Crit Care Med. 1994; 150(1), 123130.10.1164/ajrccm.150.1.8025737CrossRefGoogle ScholarPubMed
Chamson-Reig, A, Thyssen, SM, Hill, DJ, Arany, E. Exposure of the pregnant rat to low protein diet causes impaired glucose homeostasis in the young adult offspring by different mechanisms in males and females. Exp Biol Med (Maywood). 2009; 234(12), 14251436.10.3181/0902-RM-69CrossRefGoogle Scholar
Petry, CJ, Ozanne, SE, Hales, CN. Programming of intermediary metabolism. Mol Cell Endocrinol. 2001; 185, 8191.10.1016/S0303-7207(01)00627-XCrossRefGoogle ScholarPubMed
Crosby, WM. Studies in fetal malnutrition. Am J Dis Child. 1991; 145(8), 871876.Google ScholarPubMed
Den Dekker, H, Jaddoe, VWV, Reiss, I, de Jongste, JC, Duijts, L. Fetal and infant growth patterns and risk of lower lung function and asthma. Gen R Study. 2018; 197, 183192.Google ScholarPubMed
Anessi-maesano, I, Arshad, SH, Barros, H, et al. Early growth characteristics and the risk of reduced lung function and asthma : a meta-analysis. J Allergy Clin Immunol. 2015; 137, 10261035.Google Scholar
Bose, C, Van, Marter LJ, Laughon, M, et al. Fetal growth restriction and risk of chronic lung disease among infants born before the 28th week of gestation. Pediatrics. 2009; 124(3), e450e458.CrossRefGoogle ScholarPubMed
Rytter, D, Bech, BH, Frydenberg, M, Henriksen, TB, Olsen, SF. Fetal growth and cardio-metabolic risk factors in the 20-year-old offspring. Acta Obstet Gynecol Scand. 2014; 93(11), 11501159.10.1111/aogs.12463CrossRefGoogle ScholarPubMed
Barker, DJP, Martyn, CN, Osmond, C, Hales, CN, Fall, CHD. Growth in utero and serum cholesterol concentrations in adult life. Br Med J. 1993; 307(6918), 15241527.CrossRefGoogle ScholarPubMed
Nobili, V, Alisi, A, Panera, N, Agostoni, C. Low birth weight and catch-up-growth associated with metabolic syndrome: a 10 year systematic review. Pediatr Endocrinol Rev. 2008; 6, 241247.Google Scholar
Newton, KP, Feldman, HS, Chambers, CD, et al. Low and high birth weights are risk factors for nonalcoholic fatty liver disease in children. J Pediatr. 2017; 187, 141.e1146.e1.10.1016/j.jpeds.2017.03.007CrossRefGoogle ScholarPubMed
Desai, M, Hales, CN. Role of fetal and infant growth in programming metabolism in later life. Biol Rev Camb Philos Soc. 1997; 72(2), 329348.CrossRefGoogle ScholarPubMed
Kingsley, SMK, Bhat, BV. Differential paradigms in animal models of sepsis. Curr Infect Dis Rep. 2016; 18(9), 26.CrossRefGoogle ScholarPubMed
Buras, JA, Holzmann, B, Sitkovsky, M. Animal models of sepsis: setting the stage. Nat Rev Drug Discov. 2005; 4(10), 854865.10.1038/nrd1854CrossRefGoogle ScholarPubMed
Zhang, W, Ma, C, Xie, P, et al. Gut microbiota of newborn piglets with intrauterine growth restriction have lower diversity and different taxonomic abundances. J Appl Microbiol. 2019; 127(2), 354369.CrossRefGoogle ScholarPubMed
Fança-Berthon, P, Hoebler, C, Mouzet, E, David, A, Michel, C. Intrauterine growth restriction not only modifies the cecocolonic microbiota in neonatal rats but also affects its activity in young adult rats. J Pediatr Gastroenterol Nutr. 2010; 51(4), 402413.CrossRefGoogle Scholar
Malloy, J, McCaig, LM, Veldhuizen, R, et al. Alterations of the endogenous surfactant system in septic adult rats. Am J Resp Crit Care Med. 1997; 156(2 I), 617623.10.1164/ajrccm.156.2.9608009CrossRefGoogle ScholarPubMed
Malloy, JL, Veldhuizen, RAW, Lewis, JF. Effects of ventilation on the surfactant system in sepsis-induced lung injury. J Appl Physiol. 2000; 88(2), 401408.10.1152/jappl.2000.88.2.401CrossRefGoogle ScholarPubMed
Gua, Y, Patil, NK, Luan, L, Bohannon, JK, Sherwood, ER. The biology of natural killer cells during sepsis. Immunology. 2017; 153, 190202.10.1111/imm.12854CrossRefGoogle Scholar
Filatova, NA, Knyazev, NA, Skarlato, SO, Anatskaya, O V, Vinogradov, AE. Natural killer cell activity irreversibly decreases after Cryptosporidium gastroenteritis in neonatal mice. Parasite Immunol. 2018; 40, e12524.CrossRefGoogle ScholarPubMed
Kumar, V. Natural killer cells in sepsis : underprivileged innate immune cells. Eur J Cell Biol. 2019; 98(2–4), 8193.10.1016/j.ejcb.2018.12.003CrossRefGoogle ScholarPubMed
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(10), 970977.10.1016/0026-0495(86)90064-8CrossRefGoogle ScholarPubMed
Simmons, RA, Gounis, AS, Bangalore, SA, Ogata, ES. Intrauterine growth retardation: fetal glucose transport is diminished in lung but spared in brain. Pediatr Res. 1992; 31(1), 5963.CrossRefGoogle ScholarPubMed
Longo, S, Borghesi, A, Tzialla, C, Stronati, M. IUGR and infections. Early Hum Dev. 2014; 90(Suppl.1), S42S44.CrossRefGoogle ScholarPubMed
Gatford, KL, Kaur, G, Falcão-Tebas, F, et al. Exercise as an intervention to improve metabolic outcomes after intrauterine growth restriction. Am J Physiol - Endocrinol Metab. 2014; 306(9), E999E1012.CrossRefGoogle ScholarPubMed
Davenport, MH, Meah, VL, Ruchat, SM, et al. Impact of prenatal exercise on neonatal and childhood outcomes: a systematic review and meta-analysis. Br J Sports Med. 2018; 52(21), 13861396.CrossRefGoogle ScholarPubMed