In vitro-differentiated embryonic stem cells give rise to male gametes that can generate offspring mice

Dev Cell. 2006 Jul;11(1):125-32. doi: 10.1016/j.devcel.2006.05.010.


Male gametes originate from a small population of spermatogonial stem cells (SSCs). These cells are believed to divide infinitely and to support spermatogenesis throughout life in the male. Here, we developed a strategy for the establishment of SSC lines from embryonic stem (ES) cells. These cells are able to undergo meiosis, are able to generate haploid male gametes in vitro, and are functional, as shown by fertilization after intracytoplasmic injection into mouse oocytes. Resulting two-cell embryos were transferred into oviducts, and live mice were born. Six of seven animals developed to adult mice. This is a clear indication that male gametes derived in vitro from ES cells by this strategy are able to induce normal fertilization and development. Our approach provides an accessible in vitro model system for studies of mammalian gametogenesis, as well as for the development of new strategies for the generation of transgenic mice and treatment of infertility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Differentiation
  • Cell Line
  • DNA, Recombinant / genetics
  • Embryo Transfer
  • Female
  • Green Fluorescent Proteins / genetics
  • In Vitro Techniques
  • Luminescent Proteins / genetics
  • Male
  • Meiosis
  • Mice
  • Mice, Transgenic
  • Pregnancy
  • Recombinant Proteins / genetics
  • Sperm Injections, Intracytoplasmic
  • Spermatogenesis
  • Spermatogonia / cytology*
  • Spermatogonia / metabolism
  • Stem Cell Transplantation
  • Stem Cells / cytology*
  • Stem Cells / metabolism


  • DNA, Recombinant
  • Luminescent Proteins
  • Recombinant Proteins
  • enhanced green fluorescent protein
  • red fluorescent protein
  • Green Fluorescent Proteins