Specific arrests of spermatogenesis in genetically modified and mutant mice

Abstract

In naturally occurring mutant mice but also in mice genetically modified for the study of other organs, relatively often a spermatogenic arrest is seen. In a number of cases the arrests appear to be very specific causing apoptosis of germ cells at a particular step in their development, while before this step cells progress normally. These steps include: proliferation/migration of primordial germ cells, the production of differentiating spermatogonia by gonocytes, the regulation of stem cell renewal/differentiation, the differentiation of A_al into A1 spermatogonia, proliferation of A1-A4 spermatogonia, germ cell density regulation, start of meiosis, epithelial stage IV checkpoint of pachytene spermatocytes, the first meiotic division, the formation of the acrosomic vesicle in spermatids and several other steps in spermatid development. In addition, there are many mice that have not been studied in enough detail for a proper categorization. In this review an overview is given of the various mutations and genetically modified mice showing a direct effect on specific spermatogenic cell types. In addition, the relevance of these models to our understanding of the spermatogenic process is discussed.

Infertility Associated with Meiotic Failure in the <i>tremor</i> Rat (<i>tm/tm</i>) is Caused by the Deletion of <i>Spermatogenesis Associated 22</i>

“…2B), indicating that meiosis progressed into the zygotene stage and was arrested at the zygotene or pachytene stage in mutants. This spermatogenesis phenotype, known as the “meiotic arrest” phenotype, is similar to that of the repro42 homozygous mouse, which carries a nonsense mutation in Spata22 [15], and has been previously found in many types of sterile mutant mice and rats for genes related to synaptonemal complex formation, meiotic homologous recombination repair, and regulation of DNA damage checkpoint [2, 8, 10, 21]. …”

A Dominant, Recombination-Defective Allele of Dmc1 Causing Male-Specific Sterility

“…The most advanced type of germ cells were spermatocytes with nuclear chromatin characteristic of zygotene/pachytene-stage cells (Figure 1B), present in testicular seminiferous tubules at epithelial stage IV, a developmental point at which many meiotic mutants arrest [15]. Failure to progress further led to a massive degeneration of spermatocytes (Figure 1C, labeled tubule).…”

Distinct prophase arrest mechanisms in human male meiosis

“…This is probably due to the fact that most genes studied in mouse meiosis are involved in chromosome pairing and synapsis or DSB repair, processes that when disturbed will mostly lead to type I-like arrest (De Rooij and De Boer, 2003; Hamer et al, 2008; Pacheco et al, 2015). In contrast, we selected our patient samples based on testicular histology and were thus unbiased with respect to their genetic background.…”

“…In the mouse, failure to repair meiotic DSBs properly or synapse the homologous chromosomes leads to arrest during the first meiotic prophase at a specific stage of spermatogenesis, termed epithelial stage IV arrest (De Rooij and De Boer, 2003; Hamer et al, 2008). However, despite displaying spermatocyte apoptosis at the same stage of spermatogenesis, different meiotic recombination mouse mutants show different responses and cytological end-points (Barchi et al, 2005).…”