Heritable Imprinting Defect Caused by Epigenetic Abnormalities in Mouse Spermatogonial Stem Cells

Male germ cells undergo dynamic epigenetic reprogramming during fetal development, eventually establishing spermatogonial stem cells (SSCs) that can convert into pluripotent stem cells. However, little is known about the developmental potential of fetal germ cells and how they mature into SSCs. We d...

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Bibliographic Details
Published in:Biology of reproduction 2009-03, Vol.80 (3), p.518-527
Main Authors: Lee, Jiyoung, Kanatsu-Shinohara, Mito, Ogonuki, Narumi, Miki, Hiromi, Inoue, Kimiko, Morimoto, Takeshi, Morimoto, Hiroko, Ogura, Atsuo, Shinohara, Takashi
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Body Weight - genetics
Body Weight - physiology
Cells, Cultured
DNA Methylation
Embryology: invertebrates and vertebrates. Teratology
Embryonic Stem Cells - cytology
Embryonic Stem Cells - physiology
Epigenesis, Genetic - physiology
Fundamental and applied biological sciences. Psychology
Genomic Imprinting - physiology
Germ Cells - cytology
Germ Cells - physiology
Histones - genetics
Histones - metabolism
Male
Mice
Mice, Inbred ICR
Molecular embryology
Spermatogenesis - physiology
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Summary:Male germ cells undergo dynamic epigenetic reprogramming during fetal development, eventually establishing spermatogonial stem cells (SSCs) that can convert into pluripotent stem cells. However, little is known about the developmental potential of fetal germ cells and how they mature into SSCs. We developed a culture system for fetal germ cells that proliferate for long periods of time. Male germ cells from embryos 12.5-18.5 days postcoitum could expand by glial cell line-derived neurotrophic factor, a self-renewal factor for SSCs. These cells did not form teratomas, but repopulated seminiferous tubules and produced spermatogenesis, exhibiting spermatogonia potential. However, the offspring from cultured cells showed growth abnormalities and were defective in genomic imprinting. The imprinting defect persisted in both the male and female germlines for at least four generations. Moreover, germ cells in the offspring showed abnormal histone modifications and DNA methylation patterns. These results indicate that fetal germ cells have a limited ability to become pluripotent cells and lose the ability to undergo epigenetic reprogramming by in vitro culture.
ISSN:0006-3363
1529-7268
DOI:10.1095/biolreprod.108.072330