Maternal expression of the histone demethylase Kdm4a is crucial for pre-implantation development

Development. 2017 Sep 15;144(18):3264-3277. doi: 10.1242/dev.155473. Epub 2017 Aug 21.


Regulation of chromatin composition through post-translational modifications of histones contributes to transcriptional regulation and is essential for many cellular processes, including differentiation and development. KDM4A (JMJD2A) is a lysine demethylase with specificity towards di- and tri-methylated lysine 9 and lysine 36 of histone H3 (H3K9me2/me3 and H3K36me2/me3). Here, we report that Kdm4a as a maternal factor plays a key role in embryo survival and is vital for female fertility. Kdm4a-/- female mice ovulate normally with comparable fertilization but poor implantation rates, and cannot support healthy transplanted embryos to term. This is due to a role for Kdm4a in uterine function, where its loss causes reduced expression of key genes involved in ion transport, nutrient supply and cytokine signalling, which impact embryo survival. In addition, a significant proportion of Kdm4a-deficient oocytes displays a poor intrinsic ability to develop into blastocysts. These embryos cannot compete with healthy embryos for implantation in vivo, highlighting Kdm4a as a maternal effect gene. Thus, our study dissects an important dual role for maternal Kdm4a in determining faithful early embryonic development and the implantation process.

Keywords: Epigenetics; Female fertility; Histone demethylase; Maternal effect; Pre-implantation development; Transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Embryo Implantation* / genetics
  • Embryo, Mammalian / metabolism
  • Female
  • Gene Expression Regulation, Developmental
  • Genitalia, Female / metabolism
  • Histone Demethylases / metabolism*
  • Infertility, Female / genetics
  • Infertility, Female / pathology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pregnancy
  • Signal Transduction
  • Uterus / metabolism
  • Zygote / metabolism


  • Cytokines
  • Histone Demethylases
  • JMJD2A protein, mouse