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, Nardhy Gomez-Lopez

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)700-722
Number of pages23
JournalJournal of Perinatal Medicine
Volume48
Issue number7
DOIs
StatePublished - Sep 1 2020
Externally publishedYes

Keywords

  • Acute chorioamnionitis
  • Fetal inflammation
  • Funisitis
  • Host immune response
  • Infection
  • Inflammation
  • Maternal inflammation
  • Preterm birth
  • Preterm labor
  • Systemic inflammation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology

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