Unknown,Transcriptomics,Genomics,Proteomics

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Meiotic Consequences of Genetic Extension of Unsynapsed Autosomal Chromatin

ABSTRACT: We investigated the influence of extension of autosomal asynapsis on expression profiles during spermatogenesis. We used the mouse autosomal translocation T(16;17)43H (abbreviated T43H) and t12 haplotype, a natural variant of Chr 17 encompassing four adjacent non-overlapping inversions proximal to the T43H translocation breakpoint, as a model. The presence of t12 haplotype in trans to the T43H translocation resulted in stringent spermatogenic block and in more complete silencing of genes surrounding the T43H translocation break. Strikingly, silencing of the unsynapsed autosomal chromatin preceded the inactivation of the sex chromosomes (MSCI) and was apparent already in the population of pre-mid pachytene spermatocytes and testes of 15 days old males. Populations of pre-mid-pachytene spermatocytes were isolated from Ttf+/+T43H and t12+/+T43 males in three biological replicates. Their expression was compared to two biological replicates of the populations of pre-mid pachytene spermatocytes and mid-late pachytene spermatocytes obtained from C57BL/10J fertile males. Independently, testicular RNA was isolated from 15 days old Ttf+/+T43H and t12+/+T43 males in three biological replicates and the expression was compared to the testicular expression of two 15 days old C57BL/6J males.

ORGANISM(S): Mus musculus

SUBMITTER: David Homolka

PROVIDER: E-GEOD-29177 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Balanced constitutional reciprocal translocations are the most common structural chromosomal rearrangements identiï¬ed in man and pigs. Carriers are generally phenotypically normal, but such rearrangements frequently lead to reproductive disorders. In reciprocal translocation heterozygotes, the homologous regions of the normal and derivative chromosomes involved in the rearrangement pair during the prophase of the first meiotic division, thanks to the synaptonemal complex (SC), and form a particular structure called quadrivalent. In some cases, chromosomal regions (within the quadrivalent) remain unsynapsed, especially around the breakpoints, which may trigger meiosis checkpoints leading to spermatogenesis arrest at the pachytene stage. Several hypotheses have been proposed to explain such effects of pairing failure on gametogenesis. The first one is an altered transcription of the genes located on the unpaired segments. Indeed, studies conducted in mice revealed a transcriptional repression of unpaired regions by a specific mechanism called âMeiotic Silencing of Unsynapsed Chromatinâ (MSUC) in individuals with a partial or total spermatogenesis arrest (Turner et al., 2005). If some genes necessary for the proper course of meiosis are located in such unsynapsed genomic regions, MSUC may result in an arrest of the meiotic division. Secondly, associations between the âquadrivalentâ and the XY bivalent which is transcriptionally silenced by a phenomenon known as meiotic sex chromosome inactivation (MSCI, (Turner, 2007) were also observed in individuals with altered semen parameters (azoospermic or oligospemic) (Oliver-Bonet et al., 2005; Sciurano et al., 2007a, 2012). Such an association could result in a partial reactivation of the XY body (XYB) leading to the expression of some genes located on the X chromosome (Lifschytz and Lindsley, 1972), or result in the spreading of the XYB inactivation towards the autosomal segments attached to the XYB, without reactivation of the latter (Jaafar et al., 1993). Beyond the potential spermatogenesis failure mentioned above, reciprocal translocations are systematically responsible for the production of genetically unbalanced gametes. Here we report the detailed analysis of the whole meiotic process (from spermatocytes to spermatozoa) in the case of a constitutional balanced reciprocal translocation responsible for severe oligoasthenoteratospermia. Total RNA was extracted in 3 replicates from testicular biopsies control animals, from testicular biopsy of an oligospermic boar and from testicular biopsy of a severe oligo-astheno-teratospermic boar carrier of the trcp(1;14) reciprocal translocation.

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Meiotic Consequences of Genetic Extension of Unsynapsed Autosomal Chromatin

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