Intraamniotic Lipopolysaccharide Exposure Changes Cell Populations and Structure of the Ovine Fetal Thymus

Elke Kuypers; Tim G. A. M. Wolfs; Jennifer J. P. Collins; Reint K. Jellema; John P. Newnham; Matthew W. Kemp; Suhas G. Kallapur; Alan H. Jobe; Boris W. Kramer

doi:10.1177/1933719112472742

Intraamniotic Lipopolysaccharide Exposure Changes Cell Populations and Structure of the Ovine Fetal Thymus

Elke Kuypers, Tim G. A. M. Wolfs, Jennifer J. P. Collins, Reint K. Jellema, John P. Newnham, Matthew W. Kemp, Suhas G. Kallapur, Alan H. Jobe, Boris W. Kramer^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Rationale: Chorioamnionitis induces preterm delivery and acute involution of the fetal thymus which is associated with postnatal inflammatory disorders. We studied the immune response, cell composition, and architecture of the fetal thymus following intraamniotic lipopolysaccharide (LPS) exposure. Methods: Time-mated ewes received an intraamniotic injection of LPS 5, 12, or 24 hours or 2, 4, 8, or 15 days before delivery at 125 days gestational age (term = 150 days). Results: The LPS exposure resulted in decreased blood lymphocytes within 5 hours and decreased thymic corticomedullary ratio within 24 hours. Thymic interleukin 6 (IL6) and IL17 messenger RNA (mRNA) increased 5-fold 24 hours post-LPS exposure. Increased toll-like receptor 4 (TLR4) mRNA and nuclear factor B positive cells at 24 hours after LPS delivery demonstrated acute thymic activation. Both TLR4 and IL1 mRNA increased by 5-fold and the number of Foxp3-positive cells (Foxp3+ cells) decreased 15 days after exposure. Conclusion: Intraamniotic LPS exposure caused a proinflammatory response, involution, and a persistent depletion of thymic Foxp3+ cells indicating disturbance of the fetal immune homeostasis.

Original language	English
Pages (from-to)	946-956
Journal	Reproductive Sciences
Volume	20
Issue number	8
DOIs	https://doi.org/10.1177/1933719112472742
Publication status	Published - Aug 2013

Keywords

fetal inflammatory response syndrome
prematurity
immune modulation
thymic involution

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10.1177/1933719112472742

Cite this

@article{d491396b20d844aab0d7ecd049f677aa,

title = "Intraamniotic Lipopolysaccharide Exposure Changes Cell Populations and Structure of the Ovine Fetal Thymus",

abstract = "Rationale: Chorioamnionitis induces preterm delivery and acute involution of the fetal thymus which is associated with postnatal inflammatory disorders. We studied the immune response, cell composition, and architecture of the fetal thymus following intraamniotic lipopolysaccharide (LPS) exposure. Methods: Time-mated ewes received an intraamniotic injection of LPS 5, 12, or 24 hours or 2, 4, 8, or 15 days before delivery at 125 days gestational age (term = 150 days). Results: The LPS exposure resulted in decreased blood lymphocytes within 5 hours and decreased thymic corticomedullary ratio within 24 hours. Thymic interleukin 6 (IL6) and IL17 messenger RNA (mRNA) increased 5-fold 24 hours post-LPS exposure. Increased toll-like receptor 4 (TLR4) mRNA and nuclear factor B positive cells at 24 hours after LPS delivery demonstrated acute thymic activation. Both TLR4 and IL1 mRNA increased by 5-fold and the number of Foxp3-positive cells (Foxp3+ cells) decreased 15 days after exposure. Conclusion: Intraamniotic LPS exposure caused a proinflammatory response, involution, and a persistent depletion of thymic Foxp3+ cells indicating disturbance of the fetal immune homeostasis.",

keywords = "fetal inflammatory response syndrome, prematurity, immune modulation, thymic involution",

author = "Elke Kuypers and Wolfs, {Tim G. A. M.} and Collins, {Jennifer J. P.} and Jellema, {Reint K.} and Newnham, {John P.} and Kemp, {Matthew W.} and Kallapur, {Suhas G.} and Jobe, {Alan H.} and Kramer, {Boris W.}",

year = "2013",

month = aug,

doi = "10.1177/1933719112472742",

language = "English",

volume = "20",

pages = "946--956",

journal = "Reproductive Sciences",

issn = "1933-7191",

publisher = "SAGE Publications Inc.",

number = "8",

}

TY - JOUR

T1 - Intraamniotic Lipopolysaccharide Exposure Changes Cell Populations and Structure of the Ovine Fetal Thymus

AU - Kuypers, Elke

AU - Wolfs, Tim G. A. M.

AU - Collins, Jennifer J. P.

AU - Jellema, Reint K.

AU - Newnham, John P.

AU - Kemp, Matthew W.

AU - Kallapur, Suhas G.

AU - Jobe, Alan H.

AU - Kramer, Boris W.

PY - 2013/8

Y1 - 2013/8

N2 - Rationale: Chorioamnionitis induces preterm delivery and acute involution of the fetal thymus which is associated with postnatal inflammatory disorders. We studied the immune response, cell composition, and architecture of the fetal thymus following intraamniotic lipopolysaccharide (LPS) exposure. Methods: Time-mated ewes received an intraamniotic injection of LPS 5, 12, or 24 hours or 2, 4, 8, or 15 days before delivery at 125 days gestational age (term = 150 days). Results: The LPS exposure resulted in decreased blood lymphocytes within 5 hours and decreased thymic corticomedullary ratio within 24 hours. Thymic interleukin 6 (IL6) and IL17 messenger RNA (mRNA) increased 5-fold 24 hours post-LPS exposure. Increased toll-like receptor 4 (TLR4) mRNA and nuclear factor B positive cells at 24 hours after LPS delivery demonstrated acute thymic activation. Both TLR4 and IL1 mRNA increased by 5-fold and the number of Foxp3-positive cells (Foxp3+ cells) decreased 15 days after exposure. Conclusion: Intraamniotic LPS exposure caused a proinflammatory response, involution, and a persistent depletion of thymic Foxp3+ cells indicating disturbance of the fetal immune homeostasis.

AB - Rationale: Chorioamnionitis induces preterm delivery and acute involution of the fetal thymus which is associated with postnatal inflammatory disorders. We studied the immune response, cell composition, and architecture of the fetal thymus following intraamniotic lipopolysaccharide (LPS) exposure. Methods: Time-mated ewes received an intraamniotic injection of LPS 5, 12, or 24 hours or 2, 4, 8, or 15 days before delivery at 125 days gestational age (term = 150 days). Results: The LPS exposure resulted in decreased blood lymphocytes within 5 hours and decreased thymic corticomedullary ratio within 24 hours. Thymic interleukin 6 (IL6) and IL17 messenger RNA (mRNA) increased 5-fold 24 hours post-LPS exposure. Increased toll-like receptor 4 (TLR4) mRNA and nuclear factor B positive cells at 24 hours after LPS delivery demonstrated acute thymic activation. Both TLR4 and IL1 mRNA increased by 5-fold and the number of Foxp3-positive cells (Foxp3+ cells) decreased 15 days after exposure. Conclusion: Intraamniotic LPS exposure caused a proinflammatory response, involution, and a persistent depletion of thymic Foxp3+ cells indicating disturbance of the fetal immune homeostasis.

KW - fetal inflammatory response syndrome

KW - prematurity

KW - immune modulation

KW - thymic involution

U2 - 10.1177/1933719112472742

DO - 10.1177/1933719112472742

M3 - Article

C2 - 23314960

SN - 1933-7191

VL - 20

SP - 946

EP - 956

JO - Reproductive Sciences

JF - Reproductive Sciences

IS - 8

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