Pregnancy-specific transcriptional changes upon endotoxin exposure in mice

Kenichiro Motomura 1 , 2 , Roberto Romero 1 , 3 , 4 , 5 , 6 , 7 , Adi L. Tarca 1 , 2 , 8 , Jose Galaz 1 , 2 , Gaurav Bhatti 1 , 2 , Bogdan Done 1 , 2 , Marcia Arenas-Hernandez 1 , 2 , Dustyn Levenson 1 , 2 , Rebecca Slutsky 1 , Chaur-Dong Hsu 1 , 2 , 9 ,  and Nardhy Gomez-Lopez 1 , 2 , 10
  • 1 Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, Detroit, MI, USA
  • 2 Department of Obstetrics and Gynecology, Wayne State University School of Medicine, , Detroit, USA
  • 3 Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, USA
  • 4 Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, USA
  • 5 Center for Molecular Medicine and Genetics, Wayne State University, Detroit, USA
  • 6 Detroit Medical Center, Detroit, USA
  • 7 Department of Obstetrics and Gynecology, Florida International University, Miami, USA
  • 8 Department of Computer Science, Wayne State University College of Engineering, Detroit, USA
  • 9 Department of Physiology, Wayne State University School of Medicine, Detroit, USA
  • 10 Department of Biochemistry, Microbiology and Immunology, Wayne State University School of Medicine, Detroit, USA
Kenichiro Motomura
  • Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, Detroit, MI, USA
  • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, , Detroit, MI, USA
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, Roberto Romero
  • Corresponding author
  • Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, Detroit, MI, USA
  • Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA
  • Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA
  • Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA
  • Detroit Medical Center, Detroit, MI, USA
  • Department of Obstetrics and Gynecology, Florida International University, Miami, FL, USA
  • Email
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, Adi L. Tarca
  • Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, Detroit, MI, USA
  • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, , Detroit, MI, USA
  • Department of Computer Science, Wayne State University College of Engineering, Detroit, MI, USA
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, Jose Galaz
  • Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, Detroit, MI, USA
  • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, , Detroit, MI, USA
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, Gaurav Bhatti
  • Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, Detroit, MI, USA
  • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, , Detroit, MI, USA
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, Bogdan Done
  • Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, Detroit, MI, USA
  • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, , Detroit, MI, USA
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, Marcia Arenas-Hernandez
  • Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, Detroit, MI, USA
  • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, , Detroit, MI, USA
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, Dustyn Levenson
  • Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, Detroit, MI, USA
  • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, , Detroit, MI, USA
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, Rebecca Slutsky
  • Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, Detroit, MI, USA
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, Chaur-Dong Hsu
  • Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, Detroit, MI, USA
  • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, , Detroit, MI, USA
  • Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA
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and Nardhy Gomez-Lopez
  • Corresponding author
  • Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, Detroit, MI, USA
  • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, , Detroit, MI, USA
  • Department of Biochemistry, Microbiology and Immunology, Wayne State University School of Medicine, Detroit, MI, USA
  • Email
  • Search for other articles:
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Abstract

Objectives

Pregnant women are more susceptible to certain infections; however, this increased susceptibility is not fully understood. Herein, systems biology approaches were utilized to elucidate how pregnancy modulates tissue-specific host responses to a bacterial product, endotoxin.

Methods

Pregnant and non-pregnant mice were injected with endotoxin or saline on 16.5 days post coitum (n=8–11 per group). The uterus, cervix, liver, adrenal gland, kidney, lung, and brain were collected 12 h after injection and transcriptomes were measured using microarrays. Heatmaps and principal component analysis were used for visualization. Differentially expressed genes between groups were assessed using linear models that included interaction terms to determine whether the effect of infection differed with pregnancy status. Pathway analysis was conducted to interpret gene expression changes.

Results

We report herein a multi-organ atlas of the transcript perturbations in pregnant and non-pregnant mice in response to endotoxin. Pregnancy strongly modified the host responses to endotoxin in the uterus, cervix, and liver. In contrast, pregnancy had a milder effect on the host response to endotoxin in the adrenal gland, lung, and kidney. However, pregnancy did not drastically affect the host response to endotoxin in the brain.

Conclusions

Pregnancy imprints organ-specific host immune responses upon endotoxin exposure. These findings provide insight into the host-response against microbes during pregnancy.

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