Arrest of Spermatogonial Differentiation in jsd/jsd, Sl17H/Sl17H, and Cryptorchid Mice

Abstract

The nature of the spermatogenic arrest in cryptorchid C57Bl mice and in jsd/jsd and Sl17H/Sl17H mutant mice was identified by studying whole mounts of seminiferous tubules. In all three types of mice, virtually only A spermatogonia were found, topographically arranged in clones of 1 to 16 (rarely more) cells. These clonal sizes are typical for undifferentiated spermatogonia. The proportion of these cells lying in chains of more than 2 cells (50-70%) was comparable to that seen in epithelial stages VII-VIII in the normal epithelium. It is concluded that in all three types of mice, spermatogenesis is arrested at the point where the undifferentiated A spermatogonia, specifically A(al) spermatogonia, differentiate into the first generation of the differentiating-type spermatogonia, the A1 spermatogonia. The remaining A spermatogonia were proliferating, but no accumulation of spermatogonia was present, as spermatogonial apoptosis also took place. Spermatogonial clones of all sizes were seen to undergo apoptosis, but there were relatively many large apoptotic clones, indicating that the clones became more vulnerable when they became larger. In contrast to what is seen in the normal epithelium, odd-numbered clones, not composed of 2(n) cells, were present, as well as clumps of 2 or more spermatogonial nuclei in the same cytoplasm, in all three types of mice. This indicates a lack of integrity of spermatogonial clones, also observed in other situations with a relative paucity of cells on the basal membrane. It is concluded that the differentiation of the undifferentiated spermatogonia, affected in all three types of mice as well as in vitamin A-deficient animals, is a rather vulnerable point in the spermatogenic developmental pathway.

Requirement of Seminolipid in Spermatogenesis Revealed by UDP-galactose:Ceramide Galactosyltransferase-deficient Mice

“…1b), in which only undifferentiated spermatogonia and somatic cells were found in the seminiferous tubules (20,21). The result with the Kit W/W-v mice is consistent with the deficiency of seminolipid in this mutant mouse (5).…”

Dynamic expression pattern and subcellular localization of the Rhox10 homeobox transcription factor during early germ cell development

“…2B). In contrast, adult jsd testes, which still contain undifferentiated type A spermatogonia (de Rooij et al 1999), had high levels of Rhox10 mRNA (Fig. 2C).…”

“…2C), which are enriched for undifferentiated type A spermatogonia (de Rooij et al 1999), while ii) little or no Rhox10 mRNA is expressed in testes from KS and irradiated mice ( Fig. 2A and B), which lack undifferentiated type A spermatogonia.…”

“…First, we examined the expression of Rhox10 in three germ cell-deficient mouse models: i) a mouse model of Klinefelter's syndrome (KS) that has a XXY karyotype and virtually lack all germ cells in the adult testis (Swerdloff et al 2011); ii) irradiated wild-type mice, which lose spermatogonial stem cells (SSCs) and thus contain only somatic cells 5 weeks after irradiation (Zhang et al 2006); and iii) juvenile spermatogonial depletion (jsd) mice, which lack all germ cells in adult testes except for undifferentiated type A spermatogonia (A s , A pr , and A al spermatogonia) (de Rooij et al 1999). Using qRT-PCR analysis, we found that testes from adult KS mice had nearly undetectable levels of Rhox10 mRNA ( Fig.…”

MILI, a PIWI-interacting RNA-binding Protein, Is Required for Germ Line Stem Cell Self-renewal and Appears to Positively Regulate Translation

“…The requirement of intercellular signaling is exemplified by mutations in c-Kit receptors or its ligand, stem cell factor, which causes spermatogonial arrest prior to the differentiating (A 1 ) spermatogonia stage (2,3). Intercellular signaling also involves dose-sensitive regulation by Glial cell line-derived neurotrophic factor, since mice heterozygous for its gene (Gdnf) display aberrant germ line stem cell division (4).…”