Meiotic Synapsis and Gene Expression Altered by a Balanced Y-Autosome Reciprocal Translocation in an Azoospermic Pig

Abstract

Meiotic sex chromosome silencing (MSCS) has been argued as a prerequisite for normal meiotic cell division progression during the synaptic prophase I stage. Furthermore, irregular asynapsis of autosomal axes at meiosis may be encompassing the lack of transcriptional activity normally observed for the X and Y sex chromosomes. Therefore, any chromosomal rearrangement compromising the normal mechanism of MSCS and/or the contrary, the normal meiotic transcriptional activity of autosomal chromosomes, may be observed as a meiotic and concomitant spermatogenesis arrest. Previously, we have described a Y-autosome translocation t(Y;13)(p1.3;q3.3) in an azoospermic boar. Its chromosome synapsis behavior by synaptonemal complex immunostaining and FISH analyses is documented here. Histone γH2AX protein foci appeared to be located at unsynapsed chromosomal segments (e.g., X chromosome univalents or unpaired multivalent segments), although interestingly a high proportion of primary spermatocytes showed full paired synaptonemal complex-multivalent configurations which were devoid of a γH2AX focus signal, indicating meiotic chromosome silencing. RT-qPCR analysis of testicular expression showed downregulation of 3 SSC13 genes (MLH1, SOX2, UBE2B) and upregulation of SSCY genes (ZFY, SRY). The irregularity of the normal transcription pattern in case of these genes with proven roles in the testis is in agreement with the cytological observations and could contribute to the observed phenotype.

Chromosome Integrity is Required for the Initiation of Meiotic Sex Chromosome Inactivation inCaenorhabditis elegans

“…Thus, in the system studied by Turner et al the X silencing occurs in about 50% of synapsed X chromosome regions. Similarly, Mary et al reported that in a boar with translocation of chromosomes 13 and Y, about 50% of the Y and X chromosomes showed no γH2AX signal in pachytene spermatocytes nuclei 38 . Similar levels were reported by Barasc et al in a boar with translocation of chromosomes 1 and Y 35 .…”

“…Previous reports indicated that MSCI is disrupted in heterogametic cells with sex-chromosome to autosome translocations and that, in some cases, gene expression was uncoupled from the synapsis state of the translocated chromosomes 30, 34, 35, 37, 38 . This suggested that disruption of chromosome integrity prevents initiation of MSCI.…”

Molecular Cytogenetic and Y Copy Number Analysis of a Reciprocal ECAY-ECA13 Translocation in a Stallion with Complete Meiotic Arrest

“…On the other hand, while Y-autosome translocations involve different and nonhomologous autosomes in different species, a common denominator for all cases is the involvement of the Y chromosome. Therefore, and as shown by several studies [3][4][5]17,36], a more plausible explanation for meiotic arrest is the failure to properly inactivate sex chromosomes, particularly the Y chromosome. This is in line with a recently presented theory about "the persistent Y" and "meiotic executioner genes" [37].…”

“…In the general human population, based on a study of 11,148 newborn infants, the incidence of Y-autosome translocations is approximately 1/2000 [ 1 ]. In domestic animals, five cases have been reported in pigs [ 2 , 3 , 4 , 5 ], two cases in cattle [ 6 , 7 ], and one case in horses [ 8 ].…”

Meiotic Silencing in Pigs: A Case Study in a Translocated Azoospermic Boar

“…The meiotic behavior of chromosomal rearrangements has been investigated in a limited number of cases in pigs. Indeed, until now, meiotic analyses concerned only three Y-autosome [35,38,39] and one autosome-autosome translocations in this species [31]. Yautosome translocations lead to an association of autosomes with the XY body, resulting in a total arrest of spermatogenesis.…”