In vitro-differentiated embryonic stem cells give rise to male gametes that can generate offspring mice.
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.
Nayernia
Karim
K
Institute of Human Genetics, University of Göttingen, 37073 Göttingen, Germany. karim.nayernia@ncl.ac.uk
Nolte
Jessica
J
Michelmann
Hans W
HW
Lee
Jae Ho
JH
Rathsack
Kristina
K
Drusenheimer
Nadja
N
Dev
Arvind
A
Wulf
Gerald
G
Ehrmann
Ingrid E
IE
Elliott
David J
DJ
Okpanyi
Vera
V
Zechner
Ulrich
U
Haaf
Thomas
T
Meinhardt
Andreas
A
Engel
Wolfgang
W
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
D004274:DNA, Recombinant; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D011994:Recombinant Proteins; D000097573:Red Fluorescent Protein; C485184:enhanced green fluorescent protein