Fetal Immune Response to Chorioamnionitis

Suhas G. Kallapur; Pietro Presicce; Cesar M. Rueda; Alan H. Jobe; Claire A. Chougnet

doi:10.1055/s-0033-1361823

Seminars in Reproductive Medicine, Inhaltsverzeichnis

Semin Reprod Med 2014; 32(01): 056-067
DOI: 10.1055/s-0033-1361823

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Fetal Immune Response to Chorioamnionitis

Autor*innen

Suhas G. Kallapur

¹Division of Neonatology/Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati
Pietro Presicce

¹Division of Neonatology/Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati
Cesar M. Rueda

²Division of Immunobiology, The Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio
Alan H. Jobe

¹Division of Neonatology/Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati
Claire A. Chougnet

²Division of Immunobiology, The Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio

Abstract

Chorioamnionitis is a frequent cause of preterm birth and is associated with an increased risk for injury responses in the lung, gastrointestinal tract, brain, and other fetal organs. Chorioamnionitis is a polymicrobial nontraditional infectious disease because the organisms causing chorioamnionitis are generally of low virulence and colonize the amniotic fluid often for extended periods, and the host (mother and the fetus) does not have typical infection-related symptoms such as fever. In this review, we discuss the effects of chorioamnionitis in experimental animal models that mimic the human disease. Our focus is on the immune changes in multiple fetal organs and the pathogenesis of chorioamnionitis-induced injury in different fetal compartments. As chorioamnionitis disproportionately affects preterm infants, we discuss the relevant developmental context for the immune system. We also provide a clinical context for the fetal responses.

Keywords

infection - fetal inflammatory response - prematurity - animal models

Volltext

Referenzen

References
1 DiGiulio DB, Romero R, Kusanovic JP , et al. Prevalence and diversity of microbes in the amniotic fluid, the fetal inflammatory response, and pregnancy outcome in women with preterm pre-labor rupture of membranes. Am J Reprod Immunol 2010; 64 (1) 38-57
2 Gravett MG, Rubens CE, Nunes TM ; GAPPS Review Group. Global report on preterm birth and stillbirth (2 of 7): discovery science. BMC Pregnancy Childbirth 2010; 10 (Suppl. 01) S2
3 DiGiulio DB, Romero R, Amogan HP , et al. Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culture-based investigation. PLoS ONE 2008; 3 (8) e3056
4 Onderdonk AB, Delaney ML, DuBois AM, Allred EN, Leviton A ; Extremely Low Gestational Age Newborns (ELGAN) Study Investigators. Detection of bacteria in placental tissues obtained from extremely low gestational age neonates. Am J Obstet Gynecol 2008; 198 (1) e1-e7
5 Goldenberg RL, Hauth JC, Andrews WW. Intrauterine infection and preterm delivery. N Engl J Med 2000; 342 (20) 1500-1507
6 Kim MJ, Romero R, Gervasi MT , et al. Widespread microbial invasion of the chorioamniotic membranes is a consequence and not a cause of intra-amniotic infection. Lab Invest 2009; 89 (8) 924-936
7 Grigsby PL, Novy MJ, Adams Waldorf KM, Sadowsky DW, Gravett MG. Choriodecidual inflammation: a harbinger of the preterm labor syndrome. Reprod Sci 2010; 17 (1) 85-94
8 Adams Waldorf KM, Gravett MG, McAdams RM , et al. Choriodecidual group B streptococcal inoculation induces fetal lung injury without intra-amniotic infection and preterm labor in Macaca nemestrina. PLoS ONE 2011; 6 (12) e28972
9 Hirsch E, Saotome I, Hirsh D. A model of intrauterine infection and preterm delivery in mice. Am J Obstet Gynecol 1995; 172 (5) 1598-1603
10 Elovitz MA, Brown AG, Breen K, Anton L, Maubert M, Burd I. Intrauterine inflammation, insufficient to induce parturition, still evokes fetal and neonatal brain injury. Int J Dev Neurosci 2011; 29 (6) 663-671
11 Davies JK, Shikes RH, Sze CI , et al. Histologic inflammation in the maternal and fetal compartments in a rabbit model of acute intra-amniotic infection. Am J Obstet Gynecol 2000; 183 (5) 1088-1093
12 Kannan S, Saadani-Makki F, Muzik O , et al. Microglial activation in perinatal rabbit brain induced by intrauterine inflammation: detection with 11C-(R)-PK11195 and small-animal PET. J Nucl Med 2007; 48 (6) 946-954
13 Yoon BH, Kim CJ, Romero R , et al. Experimentally induced intrauterine infection causes fetal brain white matter lesions in rabbits. Am J Obstet Gynecol 1997; 177 (4) 797-802
14 Willet KE, Kramer BW, Kallapur SG , et al. Intra-amniotic injection of IL-1 induces inflammation and maturation in fetal sheep lung. Am J Physiol Lung Cell Mol Physiol 2002; 282 (3) L411-L420
15 Jobe AH, Newnham JP, Willet KE , et al. Effects of antenatal endotoxin and glucocorticoids on the lungs of preterm lambs. Am J Obstet Gynecol 2000; 182 (2) 401-408
16 Moss TJ, Nitsos I, Ikegami M, Jobe AH, Newnham JP. Experimental intrauterine ureaplasma infection in sheep. Am J Obstet Gynecol 2005; 192: 1179-1186
17 Gravett MG, Haluska GJ, Cook MJ, Novy MJ. Fetal and maternal endocrine responses to experimental intrauterine infection in rhesus monkeys. Am J Obstet Gynecol 1996; 174 (6) 1725-1731 , discussion 1731–1733
18 Novy MJ, Duffy L, Axthelm MK , et al. Ureaplasma parvum or Mycoplasma hominis as sole pathogens cause chorioamnionitis, preterm delivery, and fetal pneumonia in rhesus macaques. Reprod Sci 2009; 16 (1) 56-70
19 Sadowsky DW, Adams KM, Gravett MG, Witkin SS, Novy MJ. Preterm labor is induced by intraamniotic infusions of interleukin-1beta and tumor necrosis factor-alpha but not by interleukin-6 or interleukin-8 in a nonhuman primate model. Am J Obstet Gynecol 2006; 195 (6) 1578-1589
20 Kallapur SG, Presicce P, Senthamaraikannan P , et al. Intra-amniotic IL-1β induces fetal inflammation in rhesus monkeys and alters the regulatory T cell/IL-17 balance. J Immunol 2013; 191 (3) 1102-1109
21 Hillman NH, Moss TJ, Nitsos I , et al. Toll-like receptors and agonist responses in the developing fetal sheep lung. Pediatr Res 2008; 63 (4) 388-393
22 Ikegami M, Moss TJ, Kallapur SG , et al. Minimal lung and systemic responses to TNF-alpha in preterm sheep. Am J Physiol Lung Cell Mol Physiol 2003; 285 (1) L121-L129
23 Kallapur SG, Moss TJ, Auten Jr RL , et al. IL-8 signaling does not mediate intra-amniotic LPS-induced inflammation and maturation in preterm fetal lamb lung. Am J Physiol Lung Cell Mol Physiol 2009; 297 (3) L512-L519
24 DiGiulio DB. Diversity of microbes in amniotic fluid. Semin Fetal Neonatal Med 2012; 17 (1) 2-11
25 Paralanov V, Lu J, Duffy LB , et al. Comparative genome analysis of 19 Ureaplasma urealyticum and Ureaplasma parvum strains. BMC Microbiol 2012; 12: 88
26 Dando SJ, Nitsos I, Kallapur SG , et al. The role of the multiple banded antigen of Ureaplasma parvum in intra-amniotic infection: major virulence factor or decoy?. PLoS ONE 2012; 7 (1) e29856
27 Knox CL, Dando SJ, Nitsos I , et al. The severity of chorioamnionitis in pregnant sheep is associated with in vivo variation of the surface-exposed multiple-banded antigen/gene of Ureaplasma parvum . Biol Reprod 2010; 83 (3) 415-426
28 Xiao L, Paralanov V, Glass JI , et al. Extensive horizontal gene transfer in Ureaplasmas from humans questions the utility of serotyping for diagnostic purposes. J Clin Microbiol 2011; 49 (8) 2818-2826
29 Gerber S, Vial Y, Hohlfeld P, Witkin SS. Detection of Ureaplasma urealyticum in second-trimester amniotic fluid by polymerase chain reaction correlates with subsequent preterm labor and delivery. J Infect Dis 2003; 187 (3) 518-521
30 Perni SC, Vardhana S, Korneeva I , et al. Mycoplasma hominis and Ureaplasma urealyticum in midtrimester amniotic fluid: association with amniotic fluid cytokine levels and pregnancy outcome. Am J Obstet Gynecol 2004; 191 (4) 1382-1386
31 Bry K, Lappalainen U, Hallman M. Intraamniotic interleukin-1 accelerates surfactant protein synthesis in fetal rabbits and improves lung stability after premature birth. J Clin Invest 1997; 99 (12) 2992-2999
32 Bachurski CJ, Ross GF, Ikegami M, Kramer BW, Jobe AH. Intra-amniotic endotoxin increases pulmonary surfactant proteins and induces SP-B processing in fetal sheep. Am J Physiol Lung Cell Mol Physiol 2001; 280 (2) L279-L285
33 Newnham JP, Moss TJ, Padbury JF , et al. The interactive effects of endotoxin with prenatal glucocorticoids on short-term lung function in sheep. Am J Obstet Gynecol 2001; 185 (1) 190-197
34 Kramer BW, Kallapur SG, Moss TJ , et al. Modulation of fetal inflammatory response on exposure to lipopolysaccharide by chorioamnion, lung, or gut in sheep. Am J Obstet Gynecol 2010; 202 (1) e1-e9
35 Kemp MW, Kannan PS, Saito M , et al. Selective exposure of the fetal lung and skin/amnion (but not gastro-intestinal tract) to LPS elicits acute systemic inflammation in fetal sheep. PLoS ONE 2013; 8 (5) e63355
36 Moss TJ, Nitsos I, Kramer BW, Ikegami M, Newnham JP, Jobe AH. Intra-amniotic endotoxin induces lung maturation by direct effects on the developing respiratory tract in preterm sheep. Am J Obstet Gynecol 2002; 187 (4) 1059-1065
37 Sosenko IR, Kallapur SG, Nitsos I , et al. IL-1 alpha causes lung inflammation and maturation by direct effects on preterm fetal lamb lungs. Pediatr Res 2006; 60 (3) 294-298
38 Kallapur SG, Moss TJM, Ikegami M, Jasman RL, Newnham JP, Jobe AH. Recruited inflammatory cells mediate endotoxin-induced lung maturation in preterm fetal lambs. Am J Respir Crit Care Med 2005; 172 (10) 1315-1321
39 Kallapur SG, Nitsos I, Moss TJ , et al. IL-1 mediates pulmonary and systemic inflammatory responses to chorioamnionitis induced by lipopolysaccharide. Am J Respir Crit Care Med 2009; 179 (10) 955-961
40 Willet KE, Jobe AH, Ikegami M, Newnham J, Brennan S, Sly PD. Antenatal endotoxin and glucocorticoid effects on lung morphometry in preterm lambs. Pediatr Res 2000; 48 (6) 782-788
41 Collins JJ, Kuypers E, Nitsos I , et al. LPS-induced chorioamnionitis and antenatal corticosteroids modulate Shh signaling in the ovine fetal lung. Am J Physiol Lung Cell Mol Physiol 2012; 303 (9) L778-L787
42 Prince LS, Dieperink HI, Okoh VO, Fierro-Perez GA, Lallone RL. Toll-like receptor signaling inhibits structural development of the distal fetal mouse lung. Dev Dyn 2005; 233 (2) 553-561
43 Blackwell TS, Hipps AN, Yamamoto Y , et al. NF-κB signaling in fetal lung macrophages disrupts airway morphogenesis. J Immunol 2011; 187 (5) 2740-2747
44 Kallapur SG, Bachurski CJ, Le Cras TD, Joshi SN, Ikegami M, Jobe AH. Vascular changes after intra-amniotic endotoxin in preterm lamb lungs. Am J Physiol Lung Cell Mol Physiol 2004; 287 (6) L1178-L1185
45 Polglase GR, Hooper SB, Gill AW , et al. Intrauterine inflammation causes pulmonary hypertension and cardiovascular sequelae in preterm lambs. J Appl Physiol (1985) 2010; 108 (6) 1757-1765
46 Moss TJ, Knox CL, Kallapur SG , et al. Experimental amniotic fluid infection in sheep: effects of Ureaplasma parvum serovars 3 and 6 on preterm or term fetal sheep. Am J Obstet Gynecol 2008; 198 (1) e1-e8
47 Moss TJ, Nitsos I, Knox CL , et al. Ureaplasma colonization of amniotic fluid and efficacy of antenatal corticosteroids for preterm lung maturation in sheep. Am J Obstet Gynecol 2009; 200 (1) e1-e6
48 Collins JJ, Kallapur SG, Knox CL , et al. Inflammation in fetal sheep from intra-amniotic injection of Ureaplasma parvum . Am J Physiol Lung Cell Mol Physiol 2010; 299 (6) L852-L860
49 Bry K, Whitsett JA, Lappalainen U. IL-1beta disrupts postnatal lung morphogenesis in the mouse. Am J Respir Cell Mol Biol 2007; 36 (1) 32-42
50 Kramer BW, Joshi SN, Moss TJ , et al. Endotoxin-induced maturation of monocytes in preterm fetal sheep lung. Am J Physiol Lung Cell Mol Physiol 2007; 293 (2) L345-L353
51 Shah TA, Hillman NH, Nitsos I , et al. Pulmonary and systemic expression of monocyte chemotactic proteins in preterm sheep fetuses exposed to lipopolysaccharide-induced chorioamnionitis. Pediatr Res 2010; 68 (3) 210-215
52 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 (3) L527-L536
53 Kallapur SG, Jobe AH, Ikegami M, Bachurski CJ. Increased IP-10 and MIG expression after intra-amniotic endotoxin in preterm lamb lung. Am J Respir Crit Care Med 2003; 167 (5) 779-786
54 Wolfs TG, Buurman WA, Zoer B , et al. Endotoxin induced chorioamnionitis prevents intestinal development during gestation in fetal sheep. PLoS ONE 2009; 4 (6) e5837
55 Kunzmann S, Collins JJ, Yang Y , et al. Antenatal inflammation reduces expression of caveolin-1 and influences multiple signaling pathways in preterm fetal lungs. Am J Respir Cell Mol Biol 2011; 45 (5) 969-976
56 Kunzmann S, Speer CP, Jobe AH, Kramer BW. Antenatal inflammation induced TGF-beta1 but suppressed CTGF in preterm lungs. Am J Physiol Lung Cell Mol Physiol 2007; 292 (1) L223-L231
57 Sweet DG, Huggett MT, Warner JA , et al. Maternal betamethasone and chorioamnionitis induce different collagenases during lung maturation in fetal sheep. Neonatology 2008; 94 (2) 79-86
58 Lappalainen U, Whitsett JA, Wert SE, Tichelaar JW, Bry K. Interleukin-1beta causes pulmonary inflammation, emphysema, and airway remodeling in the adult murine lung. Am J Respir Cell Mol Biol 2005; 32 (4) 311-318
59 Biswas SK, Lopez-Collazo E. Endotoxin tolerance: new mechanisms, molecules and clinical significance. Trends Immunol 2009; 30 (10) 475-487
60 Kallapur SG, Jobe AH, Ball MK , et al. Pulmonary and systemic endotoxin tolerance in preterm fetal sheep exposed to chorioamnionitis. J Immunol 2007; 179 (12) 8491-8499
61 Kramer BW, Ikegami M, Moss TJ, Nitsos I, Newnham JP, Jobe AH. Endotoxin-induced chorioamnionitis modulates innate immunity of monocytes in preterm sheep. Am J Respir Crit Care Med 2005; 171 (1) 73-77
62 Foster SL, Hargreaves DC, Medzhitov R. Gene-specific control of inflammation by TLR-induced chromatin modifications. Nature 2007; 447 (7147) 972-978
63 Kramer BW, Kallapur SG, Moss TJ, Nitsos I, Newnham JP, Jobe AH. Intra-amniotic LPS modulation of TLR signaling in lung and blood monocytes of fetal sheep. Innate Immun 2009; 15 (2) 101-107
64 Snyder CC, Wolfe KB, Gisslen T , et al. Modulation of lipopolysaccharide-induced chorioamnionitis by Ureaplasma parvum in sheep. Am J Obstet Gynecol 2013; 208 (5) e1-e8
65 Kallapur SG, Kramer BW, Knox CL , et al. Chronic fetal exposure to Ureaplasma parvum suppresses innate immune responses in sheep. J Immunol 2011; 187 (5) 2688-2695
66 Gisslen T, Hillman NH, Musk GC, Kemp MW, Kramer BW, Senthamaraikannan P , et al. Repeated exposure to intra-amniotic LPS partially protects against adverse effects of intravenous LPS in preterm lambs. Innate Immun 2013; [Epub ahead of print]
67 Tang JR, Seedorf GJ, Muehlethaler V , et al. Moderate postnatal hyperoxia accelerates lung growth and attenuates pulmonary hypertension in infant rats after exposure to intra-amniotic endotoxin. Am J Physiol Lung Cell Mol Physiol 2010; 299 (6) L735-L748
68 Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2006; (3) CD004454
69 Banks BA, Cnaan A, Morgan MA , et al; North American Thyrotropin-Releasing Hormone Study Group. Multiple courses of antenatal corticosteroids and outcome of premature neonates. Am J Obstet Gynecol 1999; 181 (3) 709-717
70 Andrews WW, Goldenberg RL, Faye-Petersen O, Cliver S, Goepfert AR, Hauth JC. The Alabama Preterm Birth study: polymorphonuclear and mononuclear cell placental infiltrations, other markers of inflammation, and outcomes in 23- to 32-week preterm newborn infants. Am J Obstet Gynecol 2006; 195 (3) 803-808
71 Kallapur SG, Kramer BW, Moss TJ , et al. Maternal glucocorticoids increase endotoxin-induced lung inflammation in preterm lambs. Am J Physiol Lung Cell Mol Physiol 2003; 284 (4) L633-L642
72 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 (5) 1458-1466
73 Kuypers E, Collins JJ, Kramer BW , et al. Intra-amniotic LPS and antenatal betamethasone: inflammation and maturation in preterm lamb lungs. Am J Physiol Lung Cell Mol Physiol 2012; 302 (4) L380-L389
74 Wolfe KB, Snyder CC, Gisslen T , et al. Modulation of lipopolysaccharide-induced chorioamnionitis in fetal sheep by maternal betamethasone. Reprod Sci 2013; 20 (12) 1447-1454
75 Kuypers E, Collins JJ, Jellema RK , et al. Ovine fetal thymus response to lipopolysaccharide-induced chorioamnionitis and antenatal corticosteroids. PLoS ONE 2012; 7 (5) e38257
76 Kim YM, Romero R, Chaiworapongsa T, Espinoza J, Mor G, Kim CJ. Dermatitis as a component of the fetal inflammatory response syndrome is associated with activation of Toll-like receptors in epidermal keratinocytes. Histopathology 2006; 49 (5) 506-514
77 Kemp MW, Saito M, Nitsos I, Jobe AH, Kallapur SG, Newnham JP. Exposure to in utero lipopolysaccharide induces inflammation in the fetal ovine skin. Reprod Sci 2011; 18 (1) 88-98
78 Kemp MW, Saito M, Kallapur SG , et al. Inflammation of the fetal ovine skin following in utero exposure to Ureaplasma parvum . Reprod Sci 2011; 18 (11) 1128-1137
79 Cupedo T, Nagasawa M, Weijer K, Blom B, Spits H. Development and activation of regulatory T cells in the human fetus. Eur J Immunol 2005; 35 (2) 383-390
80 Darrasse-Jèze G, Marodon G, Salomon BL, Catala M, Klatzmann D. Ontogeny of CD4+CD25+ regulatory/suppressor T cells in human fetuses. Blood 2005; 105 (12) 4715-4721
81 Farley AM, Morris LX, Vroegindeweij E , et al. Dynamics of thymus organogenesis and colonization in early human development. Development 2013; 140 (9) 2015-2026
82 Galy A, Verma S, Bárcena A, Spits H. Precursors of CD3+CD4+CD8+ cells in the human thymus are defined by expression of CD34. Delineation of early events in human thymic development. J Exp Med 1993; 178 (2) 391-401
83 Lobach DF, Haynes BF. Ontogeny of the human thymus during fetal development. J Clin Immunol 1987; 7 (2) 81-97
84 Lobach DF, Hensley LL, Ho W, Haynes BF. Human T cell antigen expression during the early stages of fetal thymic maturation. J Immunol 1985; 135 (3) 1752-1759
85 Michaëlsson J, Mold JE, McCune JM, Nixon DF. Regulation of T cell responses in the developing human fetus. J Immunol 2006; 176 (10) 5741-5748
86 Josefowicz SZ, Lu LF, Rudensky AY. Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol 2012; 30: 531-564
87 Janossy G, Bofill M, Poulter LW , et al. Separate ontogeny of two macrophage-like accessory cell populations in the human fetus. J Immunol 1986; 136 (12) 4354-4361
88 Müller C, Ziegler A, Muller C , et al. Divergent expression of HLA-DC/MB, -DR, and -SB region products on normal and pathological tissues as detected by monoclonal antibodies. Immunobiology 1985; 169 (3) 228-249
89 Blom B, Res PC, Spits H. T cell precursors in man and mice. Crit Rev Immunol 1998; 18 (4) 371-388
90 Mold JE, Venkatasubrahmanyam S, Burt TD , et al. Fetal and adult hematopoietic stem cells give rise to distinct T cell lineages in humans. Science 2010; 330 (6011) 1695-1699
91 De Felice C, Latini G, Del Vecchio A, Toti P, Bagnoli F, Petraglia F. Small thymus at birth: a predictive radiographic sign of bronchopulmonary dysplasia. Pediatrics 2002; 110 (2, Pt 1) 386-388
92 De Felice C, Toti P, Santopietro R, Stumpo M, Pecciarini L, Bagnoli F. Small thymus in very low birth weight infants born to mothers with subclinical chorioamnionitis. J Pediatr 1999; 135 (3) 384-386
93 Toti P, De Felice C, Stumpo M , et al. Acute thymic involution in fetuses and neonates with chorioamnionitis. Hum Pathol 2000; 31 (9) 1121-1128
94 Di Naro E, Cromi A, Ghezzi F , et al. Fetal thymic involution: a sonographic marker of the fetal inflammatory response syndrome. Am J Obstet Gynecol 2006; 194 (1) 153-159
95 El-Haieg DO, Zidan AA, El-Nemr MM. The relationship between sonographic fetal thymus size and the components of the systemic fetal inflammatory response syndrome in women with preterm prelabour rupture of membranes. BJOG 2008; 115 (7) 836-841
96 Yinon Y, Zalel Y, Weisz B , et al. Fetal thymus size as a predictor of chorioamnionitis in women with preterm premature rupture of membranes. Ultrasound Obstet Gynecol 2007; 29 (6) 639-643
97 Jeppesen DL. The size of the thymus: an important immunological diagnostic tool?. Acta Paediatr 2003; 92 (9) 994-996
98 Kunzmann S, Glogger K, Been JV , et al. Thymic changes after chorioamnionitis induced by intraamniotic lipopolysaccharide in fetal sheep. Am J Obstet Gynecol 2010; 202 (5) e1-e9
99 Kuypers E, Wolfs TG, Collins JJ , et al. Intraamniotic lipopolysaccharide exposure changes cell populations and structure of the ovine fetal thymus. Reprod Sci 2013; 20 (8) 946-956
100 Melville JM, Bischof RJ, Meeusen EN, Westover AJ, Moss TJ. Changes in fetal thymic immune cell populations in a sheep model of intrauterine inflammation. Reprod Sci 2012; 19 (7) 740-747
101 Irla M, Hollander G, Reith W. Control of central self-tolerance induction by autoreactive CD4+ thymocytes. Trends Immunol 2010; 31 (2) 71-79
102 Anz D, Thaler R, Stephan N , et al. Activation of melanoma differentiation-associated gene 5 causes rapid involution of the thymus. J Immunol 2009; 182 (10) 6044-6050
103 Démoulins T, Abdallah A, Kettaf N , et al. Reversible blockade of thymic output: an inherent part of TLR ligand-mediated immune response. J Immunol 2008; 181 (10) 6757-6769
104 Sempowski GD, Rhein ME, Scearce RM, Haynes BF. Leukemia inhibitory factor is a mediator of Escherichia coli lipopolysaccharide-induced acute thymic atrophy. Eur J Immunol 2002; 32 (11) 3066-3070
105 Tarcic N, Ovadia H, Weiss DW, Weidenfeld J. Restraint stress-induced thymic involution and cell apoptosis are dependent on endogenous glucocorticoids. J Neuroimmunol 1998; 82 (1) 40-46
106 Stallmach T, Karolyi L. Augmentation of fetal granulopoiesis with chorioamnionitis during the second trimester of gestation. Hum Pathol 1994; 25 (3) 244-247
107 Toti P, De Felice C, Occhini R , et al. Spleen depletion in neonatal sepsis and chorioamnionitis. Am J Clin Pathol 2004; 122 (5) 765-771
108 Kallapur SG, Kramer BW, Nitsos I , et al. Pulmonary and systemic inflammatory responses to intra-amniotic IL-1α in fetal sheep. Am J Physiol Lung Cell Mol Physiol 2011; 301 (3) L285-L295
109 Lee AJ, Lambermont VA, Pillow JJ, Polglase GR, Nitsos I, Newnham JP , 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.e317-364.e324
110 Been JV, Lievense S, Zimmermann LJ, Kramer BW, Wolfs TG. Chorioamnionitis as a risk factor for necrotizing enterocolitis: a systematic review and meta-analysis. J Pediatr 2013; 162: 236-242.e232
111 Wolfs TG, Kallapur SG, Polglase GR , et al. IL-1α mediated chorioamnionitis induces depletion of FoxP3+ cells and ileal inflammation in the ovine fetal gut. PLoS ONE 2011; 6 (3) e18355
112 Wolfs TG, Kallapur SG, Knox CL , et al. Antenatal Ureaplasma infection impairs development of the fetal ovine gut in an IL-1-dependent manner. Mucosal Immunol 2013; 6 (3) 547-556
113 Yoon BH, Kim CJ, Romero R , et al. Experimentally induced intrauterine infection causes fetal brain white matter lesions in rabbits. Am J Obstet Gynecol 1997; 177 (4) 797-802
114 Burd I, Brown A, Gonzalez JM, Chai J, Elovitz MA. A mouse model of term chorioamnionitis: unraveling causes of adverse neurological outcomes. Reprod Sci 2011; 18 (9) 900-907
115 Burd I, Bentz AI, Chai J , et al. Inflammation-induced preterm birth alters neuronal morphology in the mouse fetal brain. J Neurosci Res 2010; 88 (9) 1872-1881
116 Nitsos I, Rees SM, Duncan J , et al. Chronic exposure to intra-amniotic lipopolysaccharide affects the ovine fetal brain. J Soc Gynecol Investig 2006; 13 (4) 239-247
117 Gavilanes AW, Strackx E, Kramer BW, Gantert M, Van den Hove D, Steinbusch H , et al. Chorioamnionitis induced by intraamniotic lipopolysaccharide resulted in an interval-dependent increase in central nervous system injury in the fetal sheep. Am J Obstet Gynecol 2009; 200: 437.e1-437.e8
118 Mestan K, Yu Y, Thorsen P, Skogstrand K, Matoba N, Liu X , et al. Cord blood biomarkers of the fetal inflammatory response. J Matern Fetal Neonatal Med 2009; 22 (5) 379-387
119 Zanardo V, Peruzzetto C, Trevisanuto D, Cavallin F, Vedovato S, Straface G , et al. Relationship between the neonatal white blood cell count and histologic chorioamnionitis in preterm newborns. J Matern Fetal Neonatal Med 2012; 25 (12) 2769-2772
120 Howman RA, Charles AK, Jacques A , et al. Inflammatory and haematological markers in the maternal, umbilical cord and infant circulation in histological chorioamnionitis. PLoS ONE 2012; 7 (12) e51836
121 Luciano AA, Yu H, Jackson LW, Wolfe LA, Bernstein HB. Preterm labor and chorioamnionitis are associated with neonatal T cell activation. PLoS ONE 2011; 6 (2) e16698
122 Kramer BW, Moss TJ, Willet KE , et al. Dose and time response after intra-amniotic endotoxin in preterm lambs. Am J Respir Crit Care Med 2001; 164 (6) 982-988
123 Redline RW, Faye-Petersen O, Heller D, Qureshi F, Savell V, Vogler C ; Society for Pediatric Pathology, Perinatal Section, Amniotic Fluid Infection Nosology Committee. Amniotic infection syndrome: nosology and reproducibility of placental reaction patterns. Pediatr Dev Pathol 2003; 6 (5) 435-448
124 Gomez R, Romero R, Ghezzi F, Yoon BH, Mazor M, Berry SM. The fetal inflammatory response syndrome. Am J Obstet Gynecol 1998; 179 (1) 194-202
125 Strunk T, Doherty D, Jacques A , et al. Histologic chorioamnionitis is associated with reduced risk of late-onset sepsis in preterm infants. Pediatrics 2012; 129 (1) e134-e141
126 Leviton A, Paneth N, Reuss ML , et al; Developmental Epidemiology Network Investigators. Maternal infection, fetal inflammatory response, and brain damage in very low birth weight infants. Pediatr Res 1999; 46 (5) 566-575
127 Van Marter LJ, Dammann O, Allred EN , et al; Developmental Epidemiology Network Investigators. Chorioamnionitis, mechanical ventilation, and postnatal sepsis as modulators of chronic lung disease in preterm infants. J Pediatr 2002; 140 (2) 171-176
128 Matsuda N, Hattori Y. Systemic inflammatory response syndrome (SIRS): molecular pathophysiology and gene therapy. J Pharmacol Sci 2006; 101 (3) 189-198
129 Wilson TC, Bachurski CJ, Ikegami M, Jobe AH, Kallapur SG. Pulmonary and systemic induction of SAA3 after ventilation and endotoxin in preterm lambs. Pediatr Res 2005; 58 (6) 1204-1209