Open AccessSohlh2 Knockout Mice Are Male‐Sterile Because of Degeneration of Differentiating Type A Spermatogonia
Author(s) -
Hao Jing,
Yamamoto Miwako,
Richardson Timothy E.,
Chapman Karen M.,
Denard Bray S.,
Hammer Robert E.,
Zhao Guang Quan,
Hamra F. Kent
Publication year - 2008
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2007-0502
Subject(s) - biology , spermatogenesis , germ cell , spermatocyte , sertoli cell , gonocyte , knockout mouse , microbiology and biotechnology , andrology , endocrinology , medicine , genetics , meiosis , receptor , gene
The spermatogenesis and oogenesis‐specific transcription factor Sohlh2 is normally expressed only in premeiotic germ cells. In this study, Sohlh2 and several other germ cell transcripts were found to be induced in mouse embryonic stem cells when cultured on a feeder cell line that overexpresses bone morphogenetic protein 4. To study the function of Sohlh2 in germ cells, we generated mice harboring null alleles of Sohlh2. Male Sohlh2‐deficient mice were infertile because of a block in spermatogenesis. Although normal prior to birth, Sohlh2‐null mice had reduced numbers of intermediate and type B spermatogonia by postnatal day 7. By day 10, development to the preleptotene spermatocyte stage was severely disrupted, rendering seminiferous tubules with only Sertoli cells, undifferentiated spermatogonia, and degenerating colonies of differentiating spermatogonia. Degenerating cells resembled type A2 spermatogonia and accumulated in M‐phase prior to death. A similar phenotype was observed in Sohlh2‐null mice on postnatal days 14, 21, 35, 49, 68, and 151. In adult Sohlh2‐mutant mice, the ratio of undifferentiated type A spermatogonia (DAZL+/PLZF+) to differentiating type A spermatogonia (DAZL+/PLZF−) was twice normal levels. In culture, undifferentiated type A spermatogonia isolated from Sohlh2‐null mice proliferated normally but linked the mutant phenotype to aberrant cell surface expression of the receptor‐tyrosine kinase cKit. Thus, Sohlh2 is required for progression of differentiating type A spermatogonia into type B spermatogonia. One conclusion originating from these studies would be that testicular factors normally regulate the viability of differentiating spermatogonia by signaling through Sohlh2. This regulation would provide a crucial checkpoint to optimize the numbers of spermatocytes entering meiosis during each cycle of spermatogenesis. Disclosure of potential conflicts of interest is found at the end of this article.