A High Incidence of Meiotic Silencing of Unsynapsed Chromatin Is Not Associated with Substantial Pachytene Loss in Heterozygous Male Mice Carrying Multiple Simple Robertsonian Translocations

Meiosis is a complex type of cell division that involves homologous chromosome pairing, synapsis, recombination, and segregation. When any of these processes is altered, cellular checkpoints arrest meiosis progression and induce cell elimination. Meiotic impairment is particularly frequent in organisms bearing chromosomal translocations. When chromosomal translocations appear in heterozygosis, the chromosomes involved may not correctly complete synapsis, recombination, and/or segregation, thus promoting the activation of checkpoints that lead to the death of the meiocytes. In mammals and other organisms, the unsynapsed chromosomal regions are subject to a process called meiotic silencing of unsynapsed chromatin (MSUC). Different degrees of asynapsis could contribute to disturb the normal loading of MSUC proteins, interfering with autosome and sex chromosome gene expression and triggering a massive pachytene cell death. We report that in mice that are heterozygous for eight multiple simple Robertsonian translocations, most pachytene spermatocytes bear trivalents with unsynapsed regions that incorporate, in a stage-dependent manner, proteins involved in MSUC (e.g., γH2AX, ATR, ubiquitinated-H2A, SUMO-1, and XMR). These spermatocytes have a correct MSUC response and are not eliminated during pachytene and most of them proceed into diplotene. However, we found a high incidence of apoptotic spermatocytes at the metaphase stage. These results suggest that in Robertsonian heterozygous mice synapsis defects on most pachytene cells do not trigger a prophase-I checkpoint. Instead, meiotic impairment seems to mainly rely on the action of a checkpoint acting at the metaphase stage. We propose that a low stringency of the pachytene checkpoint could help to increase the chances that spermatocytes with synaptic defects will complete meiotic divisions and differentiate into viable gametes. This scenario, despite a reduction of fertility, allows the spreading of Robertsonian translocations, explaining the multitude of natural Robertsonian populations described in the mouse

Loss of Sertoli-Germ Cell Adhesion Determines the Rapid Germ Cell Elimination During the Seasonal Regression of the Seminiferous Epithelium of the Long Hairy Armadillo Chaetophractus villosus.

The armadillo Chaetophractus villosus is a seasonal breeder whose seminiferous epithelium undergoes rapid regression with massive germ cell loss leaving the tubules with only Sertoli cells and spermatogonia. Here, we addressed the question of whether this regression entails 1) the disassembly of cell-junctions (immunolocalization of nectin-3, Cadm1, N-cadherin and beta-catenin and transmission electron microscopy, TEM); 2) apoptosis (immunolocalization of Cytochrome C and Caspase 3 and TUNEL assay) and 3) the involvement of Sertoli cells in germ cells phagocytosis (TEM). We showed a dramatic reduction in the extension of vimentin filaments associated with desmosome-like junctions at the interface between Sertoli and germ cells and an increased diffusion of the immunosignals of nectin-3, Cadm1, N-cadherin and beta-catenin. Together, these results suggest loss of Sertoli-germ cells adhesion which, in turn, might determine post-meiotic cell sloughing at the beginning of epithelium regression. Then, loss of Sertoli-germ cells adhesion triggers cell death. Cytochrome C is released from mitochondria, but whilst post-meiotic cells were negative to late apoptotic markers, at advanced regression, spermatocytes were positive to all apoptotic markers. TEM analysis showed cytoplasmic engulfment of cell debris and lipid droplets within Sertoli cells, a sign of their phagocytic activity which contributes to the elimination of the residual meiocytes still present in the latest regression phases. These findings are novel and add new players to the mechanisms of seminiferous epithelium regression occurring in seasonal breeders and introduce the armadillo as an interesting model for studying seasonal spermatogenesis