Suppressed Immune-Related Profile Rescues Abortion-Prone Fetuses: A Novel Insight Into the CBA/J × DBA/2J Mouse Model

Reprod Sci. 2019 Nov;26(11):1485-1492. doi: 10.1177/1933719119828042. Epub 2019 Feb 21.

Abstract

The adverse clinical result and poor treatment outcome in recurrent spontaneous abortion (RSA) make it necessary to understand the pathogenic mechanism. The mating combination CBA/J × DBA/2 has been widely used as an abortion-prone model compared to DBA/2-mated CBA/J mice. Here, we used RNA-seq to get a comprehensive catalogue of genes differentially expressed between survival placenta in abortion-prone model and control. Five hundred twenty-four differentially expressed genes were obtained followed by clustering analysis, Gene Ontology analysis, and pathway analysis. We paid more attention to immune-related genes namely "immune response" and "immune system process" including 33 downregulated genes and 28 upregulated genes. Twenty-one genes contribute to suppressing immune system and 7 are against it. Six genes were validated by reverse transcription-polymerase chain reaction, namely Ccr1l1, Tlr4, Tgf-β1, Tyro3, Gzmb, and Il-1β. Furthermore, Tlr4, Tgf-β1, and Il-1β were analyzed by Western blot. Such immune profile gives us a better understanding of the complicated immune processing in RSA and immunosuppression can rescue pregnancy loss.

Keywords: RNA-seq; RSA; abortion-prone model; immunosuppression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aborted Fetus / immunology*
  • Aborted Fetus / metabolism
  • Abortion, Spontaneous / genetics*
  • Abortion, Spontaneous / immunology*
  • Abortion, Spontaneous / metabolism
  • Animals
  • Disease Models, Animal*
  • Female
  • Immunity, Cellular / physiology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred CBA
  • Mice, Inbred DBA
  • Pregnancy
  • Protein Interaction Maps / physiology*
  • Random Allocation
  • Species Specificity