ETV5 is required for continuous spermatogenesis in adult mice and may mediate blood testes barrier function and testicular immune privilege - PubMed (original) (raw)
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ETV5 is required for continuous spermatogenesis in adult mice and may mediate blood testes barrier function and testicular immune privilege
Carla M K Morrow et al. Ann N Y Acad Sci. 2007 Dec.
Abstract
The transcription factor Ets-variant gene 5 (ETV5) is essential for spermatogonial stem cell (SSC) self-renewal, as the targeted deletion of the Etv5 gene in mice (Etv5(-/-)) results in only the first wave of spermatogenesis. Reciprocal transplants of neonatal germ cells from wild-type (WT) and Etv5(-/-) testes were performed to determine the role of ETV5 in Sertoli cells and germ cells. ETV5 appears to be needed in both cell types for normal spermatogenesis. In addition, Etv5(-/-) recipients displayed increased interstitial inflammation and tubular involution after transplantation. Preliminary studies suggest that the blood-testis barrier (Sertoli-Sertoli tight junctional complex) is abnormal in the Etv5(-/-) mouse.
Figures
Figure 1
Transplants from _Etv5_−/− donor mice into germ cell depleted WT testes evaluate the role of ETV5 in germ cells (a), while transplants of WT germ cells into _Etv5_−/− testes evaluates the role of ETV5 in Sertoli cells (b).
Figure 2
Testes from an _Etv5_−/− recipient that received neonatal WT germ cells (a, b, c) and an age-matched untransplanted control. (PAS/hematoxylin) a) Seminiferous tubule with spermatogenesis and bisecting basement membrane (arrow). (100x) b and c) Spermatogenesis is disorganized but contains all germ cell types, including spermatogonia (*) and elongate spermatids. (400x) (ES). d) Endogenous spermatogenesis, with no spermatogonia, is occasionally seen in older _Etv5_−/− mice. The germ cells lining the basement membrane are pre-leptotene spermatocytes. (400x)
Figure 3
_Etv5_−/− recipient testes have a severe interstitial reaction, including increased interstitial cellularity and seminiferous tubule involution. (PAS/hematoxylin; 200x)
Figure 4
Comparison of blood-testes barrier integrity in WT (a) and _Etv5_−/− (b) mice. The biotin tracer was seen throughout the interstitial space (Is) in WT and _Etv5_−/− mice. Within WT seminiferous tubules, tracer surrounded germ cells that lie below the Sertoli-Sertoli cell barrier, including spermatogonia and preleptotene spermatocytes (arrows), but the adluminal space and lumen contained no tracer (*). In _Etv5_−/− tubules, tracer was observed throughout the adluminal and luminal space (*), as well as beneath the normal region for the barrier (arrows). (400x)
References
- de Launoit Y, et al. The Ets transcription factors of the PEA3 group: Transcriptional regulators in metastasis. Biochim Biophys Acta 2006 - PubMed
- Oikawa T, Yamada T. Molecular biology of the Ets family of transcription factors. Gene. 2003;303:11–34. - PubMed
- Tyagi G, et al. Ets Variant Gene 5 (ERM) is expressed in testicular germ cells, and its effects on stem cell self-renewal may be mediated through RET In Submission.
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- K02 HD054607/HD/NICHD NIH HHS/United States
- L50 HD051287/HD/NICHD NIH HHS/United States
- R01 HD044543/HD/NICHD NIH HHS/United States
- T32 ES007326/ES/NIEHS NIH HHS/United States
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