Regulatory role of JMJD6 in placental development

Expert Rev Mol Med. 2022 Sep 19;24:e34. doi: 10.1017/erm.2022.30.


Correct placental development and function are critical to both the mother's and the foetus' health during pregnancy. Placental function depends on the correct development of the vascular network, which requires proper angiogenesis. Impaired angiogenesis in the placenta can induce foetal growth restriction, preeclampsia, and even foetal death. Placental angiogenesis is finely controlled by ubiquitous and pregnancy-specific angiogenic factors. Jumonji domain-containing protein 6 (JMJD6) is a Fe (II)- and 2-oxoglutarate (2OG)-dependent oxygenase that catalyses arginine demethylation and lysine hydroxylation of histone and non-histone peptides. JMJD6 has been implicated in embryonic development, cellular proliferation and migration, self-tolerance induction in the thymus, and adipocyte differentiation. In this review we present JMJD6's structure and activity, as well as its role in angiogenesis, oxygen sensing, and adverse pregnancy outcomes related to placental development. Understanding the interaction between JMJD6 and other placental factors may identify potential therapeutic targets for correcting abnormal placental angiogenesis and function.

Keywords: Angiogenesis; JMJD6; development; placenta; pregnancy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine / metabolism
  • Female
  • Humans
  • Jumonji Domain-Containing Histone Demethylases* / chemistry
  • Jumonji Domain-Containing Histone Demethylases* / genetics
  • Jumonji Domain-Containing Histone Demethylases* / metabolism
  • Ketoglutaric Acids / metabolism
  • Lysine / metabolism
  • Oxygen / metabolism
  • Placenta / metabolism
  • Placentation*
  • Pregnancy


  • Ketoglutaric Acids
  • Arginine
  • JMJD6 protein, human
  • Jumonji Domain-Containing Histone Demethylases
  • Lysine
  • Oxygen