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Licensed Unlicensed Requires Authentication Published by De Gruyter August 31, 2020

Pregnancy-specific transcriptional changes upon endotoxin exposure in mice

Kenichiro Motomura, Roberto Romero, Adi L. Tarca, Jose Galaz, Gaurav Bhatti, Bogdan Done, Marcia Arenas-Hernandez, Dustyn Levenson, Rebecca Slutsky, Chaur-Dong Hsu and Nardhy Gomez-Lopez

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.


Corresponding author: Nardhy Gomez-Lopez, MSc, PhD, 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, and Detroit, MI, USA; Wayne State University School of Medicine, 275 E. Hancock, Detroit, MI 48201, 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, Phone: +1 (313) 577-8904, E-mail: ; and Roberto Romero, MD, D. Med. Sci., 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, and Detroit, MI, USA; Hutzel Women’s Hospital, 3990 John R, Box 4, Detroit, MI 48201, 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, Phone: (313) 993-2700, Fax: (313) 993-2694, E-mail: .

Funding source: 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)

Funding source: NICHD/NIH/DHHS, HHSN275201300006C

Funding source: Wayne State University Perinatal Initiative in Maternal, Perinatal and Child Health

Acknowledgments

The authors are grateful to Daniel Lott for conducting the RNA extraction and the microarray experiments at the Applied Genomics Technology Center of Wayne State University in Detroit, Michigan.

  1. Research funding: This research was supported, in part, by the Perinatology Research Branch (PRB), 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), and, in part, with federal funds from the NICHD/NIH/DHHS under Contract No. HHSN275201300006C. Dr. Romero has contributed to this work as part of his official duties as an employee of the United States Federal Government. This research was also supported by the Wayne State University Perinatal Initiative in Maternal, Perinatal and Child Health.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Ethical approval: All procedures were approved by the Institutional Animal Care and Use Committee (IACUC) at Wayne State University, Detroit, MI, USA (Protocol Number A 09-08-12).

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/jpm-2020-0159).


Received: 2020-04-12
Accepted: 2020-05-27
Published Online: 2020-08-31
Published in Print: 2020-09-25

© 2020 Walter de Gruyter GmbH, Berlin/Boston

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