Low Expression of LEFTY1 in Placental Villi Is Associated with Early Unexplained Miscarriage

J Reprod Med. 2017 May-Jun;62(5-6):305-10.

Abstract

OBJECTIVE: To investigate the function and underlying mechanism of transforming growth factor–beta (TGF-β)/bone morphogenetic protein (BMP) signaling pathway in early unexplained miscarriage. STUDY DESIGN: Expression profiles of genes involved in TGF-β/BMP signaling pathway were compared between placental villous tissue samples from 2 women with missed abortion and those from 2 women with induced abortion by microarray assay. The protein expression level of the most downregulated gene—LEFTY1—was further measured using western blotting in another 8 women with missed abortion and 7 women with induced abortion. RESULTS: A total of 24 genes showed differential expression level between the 2 groups. Their functions were further investigated, of which 6 of 13 upregulated genes were TGF-β responsive genes. The most reduced gene is LEFTY1, an antagonist of TGF-β ligand. The protein expression level of LEFTY1 was confirmed to show the same trend as microarray using western blotting. CONCLUSION: A reduced expression of LEFTY1 in women with missed abortion was identified as com-pared with women with induced abortion, which may result in a dysregulation of TGF-β signaling and may be the underlying mechanism of missed abortion.

MeSH terms

  • Abortion, Missed / metabolism*
  • Adult
  • Chorionic Villi* / chemistry
  • Chorionic Villi* / metabolism
  • Female
  • Gene Expression Regulation, Developmental
  • Humans
  • Left-Right Determination Factors* / analysis
  • Left-Right Determination Factors* / genetics
  • Left-Right Determination Factors* / metabolism
  • Pregnancy

Substances

  • LEFTY1 protein, human
  • Left-Right Determination Factors