Infertility associated with incomplete spermatogenic arrest and oligozoospermia in Egr4-deficient mice

Warren G. Tourtellotte, Rakesh Nagarajan, Anthony Auyeung, Christina Mueller, Jeffrey Milbrandt*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

91 Scopus citations


Male fertility is complex and depends upon endocrine/paracrine regulatory mechanisms and morphogenetic processes occurring during testicular development, spermatogenesis (mitosis and meiosis) and spermiogenesis (spermatid maturation). Egr4 (NGFI-C, pAT133), a member of the Egr family of zinc-finger transcription factors, is thought to be involved in cellular growth and differentiation, but its specific function has been previously unknown. We derived Egr4 null mice through targeted mutagenesis and found that they were phenotypically normal with the exception that males, but not females, were infertile. Egr4 is expressed at low levels within male germ cells during meiosis and is critical for germ cell maturation during the early-mid pachytene stage. While most Egr4 null male germ cells undergo apoptosis during early-mid pachytene, some are capable of maturing beyond an apparent Egr4-dependent developmental restriction point. Consequently, a limited degree of spermiogenesis occurs but this is accompanied by markedly abnormal spermatozoon morphology and severe oligozoospermia. Egr4 appears to regulate critical genes involved in early stages of meiosis and has a singularly important role in male murine fertility. These data raise the possibility that Egr4 may contribute to some forms of human idiopathic male infertility.

Original languageEnglish (US)
Pages (from-to)5061-5071
Number of pages11
Issue number22
StatePublished - 1999


  • Egr
  • Gene targeting
  • Infertility
  • Spermatogenesis
  • Transcription factor

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology


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