Pregnancy-specific transcriptional changes upon endotoxin exposure in mice
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Kenichiro Motomura
, Adi L. Tarca
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.
Funding source: NICHD/NIH/DHHS, HHSN275201300006C
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.
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.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
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).
© 2020 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Review
- Perinatal outcomes in vanishing twin pregnancies following assisted reproductive technology (ART) – a systematic review and meta-analysis
- Mini Review
- Cervical insufficiency: a noteworthy disease with controversies
- Original Articles – Obstetrics
- Individualized birth length and head circumference percentile charts based on maternal body weight and height
- Cellular immune responses in amniotic fluid of women with a sonographic short cervix
- Comparison of buprenorphine and methadone in the management of maternal opioid use disorder in full term pregnancies
- Influence of newborn head circumference and birth weight on the delivery mode of primipara: what is more important?
- Estimated fetal weight and severe neonatal outcomes in preterm prelabor rupture of membranes
- Which technique is better to place a manoeuvrable vacuum extractor cup on the flexion point? Vacca vs. Bird technique
- Pregnancy-specific transcriptional changes upon endotoxin exposure in mice
- Effects of nifedipine on fetal cardiac function in preterm labor
- Violence against trainees: urgent ethical challenges for medical educators and academic leaders in perinatal medicine
- Original Articles – Newborns
- Comparison of image quality in brain MRI with and without MR compatible incubator and predictive value of brain MRI at expected delivery date in preterm babies
- Survey on clinical use and non-use of recombinant human erythropoietin in European neonatal units
- An alternative approach to developing guidelines for the management of an anticipated extremely preterm infant
Articles in the same Issue
- Frontmatter
- Review
- Perinatal outcomes in vanishing twin pregnancies following assisted reproductive technology (ART) – a systematic review and meta-analysis
- Mini Review
- Cervical insufficiency: a noteworthy disease with controversies
- Original Articles – Obstetrics
- Individualized birth length and head circumference percentile charts based on maternal body weight and height
- Cellular immune responses in amniotic fluid of women with a sonographic short cervix
- Comparison of buprenorphine and methadone in the management of maternal opioid use disorder in full term pregnancies
- Influence of newborn head circumference and birth weight on the delivery mode of primipara: what is more important?
- Estimated fetal weight and severe neonatal outcomes in preterm prelabor rupture of membranes
- Which technique is better to place a manoeuvrable vacuum extractor cup on the flexion point? Vacca vs. Bird technique
- Pregnancy-specific transcriptional changes upon endotoxin exposure in mice
- Effects of nifedipine on fetal cardiac function in preterm labor
- Violence against trainees: urgent ethical challenges for medical educators and academic leaders in perinatal medicine
- Original Articles – Newborns
- Comparison of image quality in brain MRI with and without MR compatible incubator and predictive value of brain MRI at expected delivery date in preterm babies
- Survey on clinical use and non-use of recombinant human erythropoietin in European neonatal units
- An alternative approach to developing guidelines for the management of an anticipated extremely preterm infant