Gestational Age-Dependent Regulation of Transthyretin in Mice during Pregnancy

Shibin Cheng, Zheping Huang, Akitoshi Nakashima, Surendra Sharma

Research output: Contribution to journalArticlepeer-review


Our prior studies have shown that protein misfolding and aggregation in the placenta are linked to the development of preeclampsia, a severe pregnancy complication. We identified transthyretin (TTR) as a key component of the aggregated protein complex. However, the regulation of native TTR in normal pregnancy remains unclear. In this study, we found that pregnant mice exhibited a remarkable and progressive decline in serum TTR levels through gestational day (gd) 12–14, followed by an increase in late pregnancy and postpartum. Meanwhile, serum albumin levels showed a modest but statistically significant increase throughout gestation. TTR protein and mRNA levels in the liver, a primary source of circulating TTR, mirrored the changes observed in serum TTR levels during gestation. Intriguingly, a similar pattern of TTR alteration was also observed in the serum of pregnant women and pregnant interleukin-10-knockout (IL-10−/−) mice with high inflammation background. In non-pregnant IL-10−/− mice, serum TTR levels were significantly lower than those in age-matched wild-type mice. Administration of IL-10 to non-pregnant IL-10−/− mice restored their serum TTR levels. Notably, dysregulation of TTR resulted in fewer implantation units, lower fetal weight, and smaller litter sizes in human TTR-overexpressing transgenic mice. Thus, TTR may play a pivotal role as a crucial regulator in normal pregnancy, and inflammation during pregnancy may contribute to the downregulation of serum TTR presence.

Original languageEnglish (US)
Article number1048
Issue number8
StatePublished - Aug 2023
Externally publishedYes


  • IL-10
  • IL-10 knockout mice
  • liver
  • placenta
  • pregnancy
  • protein aggregation
  • transthyretin

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology
  • General Agricultural and Biological Sciences


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