Evolution and function of the uterine serpins (SERPINA14)

Am J Reprod Immunol. 2010 Oct;64(4):265-74. doi: 10.1111/j.1600-0897.2010.00901.x. Epub 2010 Jul 29.


Uterine serpins (recently designated as SERPINA14) are hormonally induced proteins secreted in large quantities by the endometrial epithelium during pregnancy. The SERPINA14 proteins belong to the serine proteinase inhibitor (serpin) superfamily, but their apparent lack of inhibitory activity toward serine proteinases suggests that these proteins evolved a different function from the anti-proteinase activity typically found in most members of the serpin superfamily. The gene is present in a limited group of mammals in the Laurasiatheria superorder (ruminants, horses, pigs, dolphins and some carnivores) while being absent in primates, rodents, lagomorphs and marsupials. Thus, the gene is likely to have evolved by gene duplication after divergence of Laurasiatheria and to play an important role in pregnancy. That role may vary between species. In sheep, SERPINA14 probably serves an immunoregulatory role to prevent rejection of the fetal allograft. It is inhibitory to lymphocyte proliferation and natural killer cell function. In the pig, SERPINA14 is involved in iron transport to the fetus by binding to and stabilizing the iron-binding protein uteroferrin. It is possible that SERPINA14 has undergone divergence in function since the original emergence of the gene in a common ancestor of species possessing SERPINA14.

Publication types

  • Review

MeSH terms

  • Animals
  • Animals, Domestic
  • Endometrium / metabolism*
  • Evolution, Molecular*
  • Female
  • Fetus / immunology
  • Fetus / physiology*
  • Gene Expression Regulation
  • Mammals / genetics
  • Mammals / immunology
  • Mammals / metabolism
  • Mammals / physiology*
  • Placenta / physiology
  • Pregnancy
  • Pregnancy, Animal* / immunology
  • Pregnancy, Animal* / metabolism
  • Pregnancy, Animal* / physiology
  • Progesterone / immunology
  • Serine Proteinase Inhibitors / metabolism
  • Serpins / chemistry
  • Serpins / genetics*
  • Serpins / physiology*
  • Uterus / metabolism*


  • Serine Proteinase Inhibitors
  • Serpins
  • Progesterone