title: In vitro-differentiated embryonic stem cells give rise to male gametes that can generate offspring mice.
abstract: 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.
authors.affiliation: Institute of Human Genetics, University of Göttingen, 37073 Göttingen, Germany. karim.nayernia@ncl.ac.uk
authors.forename: Karim
authors.initials: K
authors.lastname: Nayernia
authors.forename: Jessica
authors.initials: J
authors.lastname: Nolte
authors.forename: Hans W
authors.initials: HW
authors.lastname: Michelmann
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Kristina
authors.initials: K
authors.lastname: Rathsack
authors.forename: Nadja
authors.initials: N
authors.lastname: Drusenheimer
authors.forename: Arvind
authors.initials: A
authors.lastname: Dev
authors.forename: Gerald
authors.initials: G
authors.lastname: Wulf
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Ehrmann
authors.forename: David J
authors.initials: DJ
authors.lastname: Elliott
authors.forename: Vera
authors.initials: V
authors.lastname: Okpanyi
authors.forename: Ulrich
authors.initials: U
authors.lastname: Zechner
authors.forename: Thomas
authors.initials: T
authors.lastname: Haaf
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinhardt
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Engel
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D004274:DNA, Recombinant / Q000235:genetics; D004624:Embryo Transfer; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D008540:Meiosis; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D011994:Recombinant Proteins / Q000235:genetics; D020554:Sperm Injections, Intracytoplasmic; D013091:Spermatogenesis; D013093:Spermatogonia / Q000166:cytology* / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D000097573:Red Fluorescent Protein
chemical_list: D004274:DNA, Recombinant; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D011994:Recombinant Proteins; D000097573:Red Fluorescent Protein; C485184:enhanced green fluorescent protein