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RESEARCH PRODUCT

In Vitro-Differentiated Embryonic Stem Cells Give Rise to Male Gametes that Can Generate Offspring Mice

Thomas HaafAndreas MeinhardtNadja DrusenheimerH. W. MichelmannKristina RathsackWolfgang EngelIngrid EhrmannUlrich ZechnerGerald WulfJae Ho LeeKarim NayerniaJessica NolteDavid J. ElliottArvind DevVera Okpanyi

subject

MaleGreen Fluorescent ProteinsPopulationDNA RecombinantDEVBIOMice TransgenicIn Vitro TechniquesBiologyGeneral Biochemistry Genetics and Molecular BiologyCell LineMice03 medical and health sciences0302 clinical medicinePregnancymedicineAnimalsSperm Injections IntracytoplasmicSpermatogenesiseducationMolecular BiologyGametogenesis030304 developmental biology0303 health scienceseducation.field_of_study030219 obstetrics & reproductive medicineBase SequenceStem CellsCell DifferentiationEmbryoCell BiologyEmbryo TransferSTEMCELLEmbryonic stem cellRecombinant ProteinsSpermatogoniaCell biologyLuminescent ProteinsMeiosismedicine.anatomical_structureImmunologyGameteFemalePloidyStem cellSpermatogenesisStem Cell TransplantationDevelopmental Biology

description

SummaryMale 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.

https://doi.org/10.1016/j.devcel.2006.05.010