The role of asynapsis in human spermatocyte failure

Abstract

The basic molecular mechanisms by which chromosomal rearrangements in heterozygous state produce spermatogenic disturbances are poorly understood. Testicular biopsies from five patients - one carrier of a Robertsonian translocation rob t(13;14), two carriers of two different Y-autosome translocations, a t(Y;6) and a t(Y;11), one carrier of a reciprocal translocation t(3;13) and one carrier of a heterochromatin duplication in chromosome 9 - were processed for histopathological analysis, electron microscopy and fluorescent immunolocalization of meiotic proteins. In all the patients, the asynaptic regions during pachytene are labelled by BRCA1 and retained RAD51 foci. The variant histone γ-H2AX is located on the chromatin domains of the asynaptic regions and the XY body. In contrast, these meiotic proteins are absent in those chromosomal segments that are non-homologously synapsed. The present observations on five new cases and a review of recent studies show that the common features shared by all these cases are the abnormal location of some meiotic proteins and the presence of transcriptionally silenced chromatin domains on asynaptic regions. The frequent association of these silenced regions with the XY body and the rescue of spermatocyte viability through non-homologous synapsis are also shared by all these carriers. A passive, random mechanism of clustering of asynaptic regions with the XY body is suggested.

Altered segregation pattern and numerical chromosome abnormalities interrelate in spermatozoa from Robertsonian translocation carriers

“…It has been related to the presence of asynaptic regions during trivalent formation in prophase I, which trigger the activation of the pachytene checkpoint. Heterosynapsis appears as a rescue mechanism to avoid asynapsis and it has been seen to occur preferentially between the trivalent and the sex chromosomes as well as between the trivalent and other acrocentric chromosomes (Guichaoua et al, 1990;Johanisson et al, 1987;Luciani et al, 1984;Navarro et al, 1991;Sciurano et al, 2007Sciurano et al, , 2011. Nevertheless, the occurrence of heterosynapsis during prophase I might predispose chromosomes to non-disjunction at anaphase I (Kurahashi et al, 2012;Sciurano et al, 2011;Tepperberg et al, 1999), and thus produce cells with numerical anomalies.…”

“…Heterosynapsis appears as a rescue mechanism to avoid asynapsis and it has been seen to occur preferentially between the trivalent and the sex chromosomes as well as between the trivalent and other acrocentric chromosomes (Guichaoua et al, 1990;Johanisson et al, 1987;Luciani et al, 1984;Navarro et al, 1991;Sciurano et al, 2007Sciurano et al, , 2011. Nevertheless, the occurrence of heterosynapsis during prophase I might predispose chromosomes to non-disjunction at anaphase I (Kurahashi et al, 2012;Sciurano et al, 2011;Tepperberg et al, 1999), and thus produce cells with numerical anomalies. A recent review reported that more than half of Robertsonian translocation carriers produce significantly increased percentages of gametes with numerical abnormalities unrelated to the rearranged chromosomes (Anton et al, 2011), which is an even higher frequency than that observed in reciprocal translocations and inversion carriers.…”

Variation of Meiotic Recombination Rates and MLH1 Foci Distribution in Spermatocytes of Cattle, Sheep and Goats

“…The physical link between homologous chromosomes, mediated by crossing over, serves as a bond which helps paired chromosomes to align properly in the meiotic metaphase plate and segregate correctly to the opposite sides of the dividing cell, thus providing balanced gametes [Hassold et al, 2000;Cohen et al, 2006;Coop and Przeworski, 2007]. In mammalian males, disruption of chromosome pairing and inability to execute crossing over is usually connected with a complete failure to produce viable gametes [Sciurano et al, 2012].Regardless of the importance of recombination, our knowledge of the mechanism which determines the number and position of crossover (CO) foci along chromo- …”

Altered bivalent positioning in metaphase I human spermatocytes from Robertsonian translocation carriers

“…Ta b l e 2 S i g n i f i c a n t b i v a l e n t p a i r s a s s o c i a t i o n s o f MI,22,XY,III(13q14q) (n = 41) and MI,22,XY,III(14q15q) (n = 15) Note: global mean = 0.152; 95 % CI = [0.147-0.157] a Significant bivalent pairs coinciding with those described in normal karyotypes [21] There are different non-mutually exclusive possibilities to explain such variations. Studies in Robertsonian translocation carriers have described that the reorganized chromosomes usually show asynaptic regions at pachytene which are often associated with asynaptic regions of other bivalents [40][41][42][43][44][45]. It has also been described that asynaptic regions suffer heterochromatinization and gene silencing [31,46].…”