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Male differentiation of germ cells induced by embryonic age-specific Sertoli cells in mice.
- Source :
-
Biology of reproduction [Biol Reprod] 2012 Apr 12; Vol. 86 (4), pp. 112. Date of Electronic Publication: 2012 Apr 12 (Print Publication: 2012). - Publication Year :
- 2012
-
Abstract
- Retinoic acid (RA) is a meiosis-inducing factor. Primordial germ cells (PGCs) in the developing ovary are exposed to RA, resulting in entry into meiosis. In contrast, PGCs in the developing testis enter mitotic arrest to differentiate into prospermatogonia. Sertoli cells express CYP26B1, an RA-metabolizing enzyme, providing a simple explanation for why XY PGCs do not initiate meios/is. However, regulation of entry into mitotic arrest is likely more complex. To investigate the mechanisms that regulate male germ cell differentiation, we cultured XX and XY germ cells at 11.5 and 12.5 days postcoitus (dpc) with an RA receptor inhibitor. Expression of Stra8, a meiosis initiation gene, was suppressed in all groups. However, expression of Dnmt3l, a male-specific gene, during embryogenesis was elevated but only in 12.5-dpc XY germ cells. This suggests that inhibiting RA signaling is not sufficient for male germ cell differentiation but that the male gonadal environment also contributes to this pathway. To define the influence of Sertoli cells on male germ cell differentiation, Sertoli cells at 12.5, 15.5, and 18.5 dpc were aggregated with 11.5 dpc PGCs, respectively. After culture, PGCs aggregated with 12.5 dpc Sertoli cells increased Nanos2 and Dnmt3l expression. Furthermore, these PGCs established male-specific methylation imprints of the H19 differentially methylated domains. In contrast, PGCs aggregated with Sertoli cells at late embryonic ages did not commit to the male pathway. These findings suggest that male germ cell differentiation is induced both by inhibition of RA signaling and by molecule(s) production by embryonic age-specific Sertoli cells.
- Subjects :
- Adaptor Proteins, Signal Transducing
Animals
Carrier Proteins metabolism
Cell Differentiation
DNA Methylation
DNA Modification Methylases metabolism
Female
Gene Expression Profiling
Gene Expression Regulation, Developmental
Male
Meiosis physiology
Mice
Mitosis genetics
RNA-Binding Proteins
Receptors, Retinoic Acid antagonists & inhibitors
Signal Transduction
Gametogenesis genetics
Germ Cells cytology
Proteins metabolism
Sertoli Cells physiology
Tretinoin physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-7268
- Volume :
- 86
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biology of reproduction
- Publication Type :
- Academic Journal
- Accession number :
- 22262692
- Full Text :
- https://doi.org/10.1095/biolreprod.111.095943