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Nature of the spermatogenic arrest in Dazl -/- mice
B H Schrans-Stassen1, P T Saunders, H J Cooke
1Department of Cell Biology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
Abstract:
Dazl encodes an RNA-binding protein essential for spermatogenesis. Mice that are deficient for Dazl are infertile, lacking any formation of spermatozoa, and the only germ cells present are spermatogonia and a few spermatocytes. To gain more insight regarding the timing of the spermatogenic arrest in Dazl -/- mice, we studied the spermatogonial cell types present in testis sections and in seminiferous tubular whole mounts. Most of the seminiferous tubular cross-sections contained A spermatogonia as the most advanced cell type, with only very few containing cells up to pachytene spermatocytes. Both 5-bromodeoxy-uridine incorporation and mitotic index indicated that the remaining A spermatogonia were actively proliferating. C-kit immunohistochemical studies showed that most of the A spermatogonia were positively stained for the c-Kit protein ( approximately 80%). The clonal composition of the A spermatogonia in tubular whole mounts indicated these cells to be A(single) (A(s)), A(paired) (A(pr)), and A(aligned) (A(al)) spermatogonia. It is concluded that the prime spermatogenic defect in the Dazl -/- mice is a failure of the great majority of the A(al) spermatogonia to differentiate into A(1) spermatogonia. As a result, most seminiferous tubules of Dazl -/- mice only contain actively proliferating A(s), A(pr), and A(al) spermatogonia, with cell production being equaled by apoptosis of these cells.
Insights
Dazl deficiency in mice causes infertility by arresting spermatogenesis. The primary defect is the failure of A(al) spermatogonia to differentiate, leading to their proliferation and apoptosis.
Area of Science:
- Reproductive Biology
- Developmental Biology
- Genetics
Background:
- Dazl is an RNA-binding protein crucial for male germ cell development.
- Dazl-deficient mice exhibit infertility with a complete absence of spermatozoa.
- Germ cells in Dazl-deficient mice are arrested at the spermatogonia and early spermatocyte stages.
Purpose of the Study:
- To precisely determine the timing and nature of spermatogenic arrest in Dazl-deficient mice.
- To investigate the proliferation and differentiation status of spermatogonial populations in Dazl-deficient testes.
Main Methods:
- Analysis of testis sections and seminiferous tubular whole mounts.
- Cell proliferation assessment using 5-bromodeoxyuridine incorporation and mitotic index.
- Immunohistochemical staining for c-Kit to identify spermatogonial subtypes.
- Clonal analysis of spermatogonia in whole mounts.
Main Results:
- Seminiferous tubules primarily contain A spermatogonia, with rare pachytene spermatocytes.
- A spermatogonia in Dazl-deficient mice show active proliferation and approximately 80% express c-Kit.
- Spermatogonial populations consist of A(single), A(paired), and A(aligned) types.
- The main defect identified is the failure of A(aligned) spermatogonia to differentiate into A(1) spermatogonia.
Conclusions:
- The critical defect in Dazl-deficient mice is the block in A(aligned) spermatogonial differentiation.
- This differentiation failure results in sustained proliferation and subsequent apoptosis of early spermatogonia.
- Dazl is essential for the progression of spermatogenesis beyond the A(aligned) spermatogonia stage.