Oocyte heterogeneity with respect to the meiotic silencing of unsynapsed X chromosomes in the XY female mouse

Abstract

In the XY pachytene spermatocyte, the sex chromosomes do not synapse except for the pseudoautosomal region and become transcriptionally silenced. It has been suggested that the meiotic silencing of unsynapsed chromatin (MSUC) also occurs in oocytes. In the XY sex-reversed female mouse, the sex chromosomes fail to pair in the majority of oocytes and a greater number of oocytes are eliminated during the meiotic prophase compared to the XX female. Yet, many XY oocytes survive to reach the second meiotic metaphase. The goal of our current study was to determine whether the single X chromosome shows the characteristics of asynapsis and meiotic silencing in a proportion of XY oocytes, which can explain the survival of the remaining oocytes. We first examined the accumulation of markers associated with asynapsis or transcriptional silencing, i.e., BRCA1, γH2AX, H3K9me3, and H3K27me3, at the single X chromosome in the XY oocyte. We found that γH2AX and BRCA1 were enriched on the single X chromosome whereas H3K9me3 was not, and H3K27me3 was enriched at all chromosomes in the majority of XY oocytes. We next examined the meiotic silencing of the single X chromosome using enrichment of the X-encoded ATRX protein. On average, ATRX enrichment was lower in XY oocytes than in XX oocytes as expected from its half gene dosage. However, the intensity of ATRX staining in XY oocytes harboring γH2AX domains showed a remarkable heterogeneity. We conclude that MSUC occurs with varying consequences, resulting in a heterogeneous population of oocytes with respect to protein enrichment in the XY female mouse.

Germ cell-intrinsic effects of sex chromosomes on early oocyte differentiation in mice

“…In XY oocytes, the sex chromosomes were separated, with the exception that 1 of the 66 oocytes showed paired sex chromosomes ( Fig 4B). The rare pairing of the sex chromosomes in XY oocytes is consistent with a previous result showing rare formation of the XY body in the XY TIR female [20,21]. Interestingly, the pairing rate of autosomes was not different between XX, XO and XY oocytes, whereas the sex chromosomes were more prone to mispairing than autosomes even in XX oocytes ( Fig 4C).…”

Staged developmental mapping and X chromosome transcriptional dynamics during mouse spermatogenesis

“…Our discovery that H3K9me3 is enriched during meiosis at spermatid-specific genes suggests a stronger, targeted repression in spermatocytes for a key subset of X-linked genes. The deposition of H3K9me3 615 is specific to MSCI in males, and is not observed during general meiotic silencing of unpaired chromosomes (MSUC) (Cloutier et al, 2016;Taketo and Naumova, 2013;Turner et al, 2004b). Interestingly, when comparing the levels of meiotic silencing for the X chromosome in spermatocytes with the unpaired X chromosome in XO oocytes, the transcriptional silencing was stronger in males compared to females (Cloutier et al, 2016).…”

Sex chromosome quadrivalents in oocytes of the African pygmy mouse Mus minutoides that harbors non-conventional sex chromosomes

“…The mechanism of transcriptional silencing of unsynapsed chromosomes appears to be active in M. minutoides pachytene oocytes, as inferred from BRCA1 and γH2AX staining. However, in M. musculus, this transcriptional silencing is less efficient in oocytes than in spermatocytes (Taketo and Naumova 2013;Cloutier et al 2016), and it cannot be excluded that the expression level of X-linked genes from unsynapsed X* is sufficient. Alternatively, expression of Y-linked genes from synapsed Y chromosome could be sufficiently reduced, or harmless in M. minutoides X*Y oocytes.…”

“…The chromosomal regions that remain asynapsed undergo transcriptional silencing from the pachytene stage onward, while the genes situated in synapsed regions escape silencing, even when they are engaged in non-homologous synapsis that associates not This article is part of a Special Issue on Recent advances in meiosis from DNA replication to chromosome segregation Bedited by Valérie Borde and Francesca Cole, co-edited by Paula Cohen and Scott Keeney.Ê lectronic supplementary material The online version of this article (https://doi.org/10.1007/s00412-019-00699-4) contains supplementary material, which is available to authorized users. homologous chromosomal regions (Baarends et al 2005;Turner et al 2005;Taketo and Naumova 2013;Cloutier et al 2016). In Mus musculus females (i.e., the house mouse), the inappropriate transcriptional silencing of genes essential for gametogenesis in asynapsed chromosomal regions could be the main single cause of elimination of diplotene stage oocytes with synapsis defects (Cloutier et al 2015).…”