The Experts below are selected from a list of 264 Experts worldwide ranked by ideXlab platform
Ian R. Adams - One of the best experts on this subject based on the ideXlab platform.
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Defects in meiotic recombination delay progression through pachytene in Tex19.1^−/− mouse Spermatocytes
Chromosoma, 2018Co-Authors: James H. Crichton, David Read, Ian R. AdamsAbstract:Recombination, synapsis, chromosome segregation and gene expression are co-ordinately regulated during meiosis to ensure successful execution of this specialised cell division. Studies with multiple mutant mouse lines have shown that mouse Spermatocytes possess quality control checkpoints that eliminate cells with persistent defects in chromosome synapsis. In addition, studies on Trip13 ^ mod/mod mice suggest that pachytene Spermatocytes that successfully complete chromosome synapsis can undergo meiotic arrest in response to defects in recombination. Here, we present additional support for a meiotic recombination-dependent checkpoint using a different mutant mouse line, Tex19.1 ^ −/− . The appearance of early recombination foci is delayed in Tex19.1 ^ −/− Spermatocytes during leptotene/zygotene, but some Tex19.1 ^ −/− Spermatocytes still successfully synapse their chromosomes and we show that these Spermatocytes are enriched for early recombination foci. Furthermore, we show that patterns of axis elongation, chromatin modifications and histone H1t expression are also all co-ordinately skewed towards earlier substages of pachytene in these autosomally synapsed Tex19.1 ^ −/− Spermatocytes. We also show that this skew towards earlier pachytene substages occurs in the absence of elevated Spermatocyte death in the population, that Spermatocytes with features of early pachytene are present in late stage Tex19.1 ^ −/− testis tubules and that the delay in histone H1t expression in response to loss of Tex19.1 does not occur in a Spo11 mutant background. Taken together, these data suggest that a recombination-dependent checkpoint may be able to modulate pachytene progression in mouse Spermatocytes to accommodate some types of recombination defect.
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Defects in meiotic recombination delay progression through pachytene in Tex19.1-/- mouse Spermatocytes.
Chromosoma, 2018Co-Authors: James H. Crichton, David Read, Ian R. AdamsAbstract:Recombination, synapsis, chromosome segregation and gene expression are co-ordinately regulated during meiosis to ensure successful execution of this specialised cell division. Studies with multiple mutant mouse lines have shown that mouse Spermatocytes possess quality control checkpoints that eliminate cells with persistent defects in chromosome synapsis. In addition, studies on Trip13mod/mod mice suggest that pachytene Spermatocytes that successfully complete chromosome synapsis can undergo meiotic arrest in response to defects in recombination. Here, we present additional support for a meiotic recombination-dependent checkpoint using a different mutant mouse line, Tex19.1-/-. The appearance of early recombination foci is delayed in Tex19.1-/- Spermatocytes during leptotene/zygotene, but some Tex19.1-/- Spermatocytes still successfully synapse their chromosomes and we show that these Spermatocytes are enriched for early recombination foci. Furthermore, we show that patterns of axis elongation, chromatin modifications and histone H1t expression are also all co-ordinately skewed towards earlier substages of pachytene in these autosomally synapsed Tex19.1-/- Spermatocytes. We also show that this skew towards earlier pachytene substages occurs in the absence of elevated Spermatocyte death in the population, that Spermatocytes with features of early pachytene are present in late stage Tex19.1-/- testis tubules and that the delay in histone H1t expression in response to loss of Tex19.1 does not occur in a Spo11 mutant background. Taken together, these data suggest that a recombination-dependent checkpoint may be able to modulate pachytene progression in mouse Spermatocytes to accommodate some types of recombination defect.
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Defects in Meiotic Recombination Delay Progression Through Pachytene in Mouse Spermatocytes
2017Co-Authors: James H. Crichton, David Read, Ian R. AdamsAbstract:During meiosis, recombination, synapsis, chromosome segregation and gene expression are co-ordinately regulated to ensure successful execution of this specialised cell division. In many model organisms, checkpoint controls can delay meiotic progression to allow defects or errors in these processes to be repaired or corrected. Mouse Spermatocytes possess quality control checkpoints that eliminate cells with persistent irreparable defects in chromosome synapsis or recombination, and here we show that a Spermatocyte checkpoint regulates progression through pachytene to accommodate delays in meiotic recombination. We have previously show that the appearance of early recombination foci is delayed in Tex19.1 -/- Spermatocytes during leptotene/zygotene, but some Tex19.1 -/- Spermatocytes still successfully synapse their chromosomes. Therefore, we have used autosomally synapsed Tex19.1 -/- mouse Spermatocytes to assess the consequences of delayed recombination on progression through pachytene. We show that these pachytene Spermatocytes are enriched for early recombination foci. This skew is not accompanied by cell death and likely reflects delays in the generation and/or maturation of recombination foci. Moreover, patterns of axis elongation, chromatin modifications, and histone H1t expression are also all skewed towards earlier substages of pachytene suggesting these events are co-ordinately regulated. Importantly, the delay in histone H1t expression in response to loss of Tex19.1 does not occur in a Spo11 mutant background, suggesting that histone H1t expression is being delayed by a recombination-dependent checkpoint. These data indicate that a recombination-dependent checkpoint operates in mouse Spermatocytes that can alter progression through pachytene to accommodate Spermatocytes with some types of recombination defect.
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Tex19.1 promotes Spo11-dependent meiotic recombination in mouse Spermatocytes - Fig 5
2017Co-Authors: James H. Crichton, David Read, Christopher J. Playfoot, Marie Maclennan, Howard J. Cooke, Ian R. AdamsAbstract:Tex19.1-/- Spermatocytes Have No Overt Defects in MEI4 Localisation or in H3K4me3 Accumulation at Recombination Hotspots. (A) Immunostaining of Spermatocyte chromosome spreads for the SC components SYCP3 (red) to identify leptotene nuclei and fragments of chromosome axes, and MEI4 (green). Scale bar 10 μm. (B) Quantification of MEI4 foci in leptotene Spermatocytes (218±12 for Tex19.1+/±, 223±10 for Tex19.1-/-, n = 48, 72 from three mice per genotype). Means are indicated with horizontal bars, ns indicates no significant difference (Mann-Whitney U test). (C) Immunostaining of Spermatocyte chromosome spreads for the SC components SYCP3 (red) and SYCE2 (blue) to identify leptotene nuclei, and H3K4me3 (green). Scale bar 10 μm. (D) Quantification of anti-H3K4me3 staining intensity (1648±202 and 1689±187 arbitrary units respectively, n = 21, 18 from three mice per genotype). Means are indicated with horizontal bars, ns indicates no significant difference (Mann-Whitney U test). (E, F) H3K4me3 chromatin immunoprecipitation (ChIP) from P16 Tex19.1+/± and Tex19.1-/- testes. qPCR for recombination hotspots (E) and retrotransposon sequences (F) was performed on H3K4me3 ChIP and abundance measured relative to input chromatin, then normalised to enrichment for the β-actin (Actb) transcriptional start site (TSS). Mean normalised enrichment ± standard error from three animals of each genotype is shown. Polr2a and Gapdh TSSs were used as positive controls, and an intragenic region of Polr2a as a negative control. ns indicates no significant difference, * indicates p
James H. Crichton - One of the best experts on this subject based on the ideXlab platform.
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Defects in meiotic recombination delay progression through pachytene in Tex19.1^−/− mouse Spermatocytes
Chromosoma, 2018Co-Authors: James H. Crichton, David Read, Ian R. AdamsAbstract:Recombination, synapsis, chromosome segregation and gene expression are co-ordinately regulated during meiosis to ensure successful execution of this specialised cell division. Studies with multiple mutant mouse lines have shown that mouse Spermatocytes possess quality control checkpoints that eliminate cells with persistent defects in chromosome synapsis. In addition, studies on Trip13 ^ mod/mod mice suggest that pachytene Spermatocytes that successfully complete chromosome synapsis can undergo meiotic arrest in response to defects in recombination. Here, we present additional support for a meiotic recombination-dependent checkpoint using a different mutant mouse line, Tex19.1 ^ −/− . The appearance of early recombination foci is delayed in Tex19.1 ^ −/− Spermatocytes during leptotene/zygotene, but some Tex19.1 ^ −/− Spermatocytes still successfully synapse their chromosomes and we show that these Spermatocytes are enriched for early recombination foci. Furthermore, we show that patterns of axis elongation, chromatin modifications and histone H1t expression are also all co-ordinately skewed towards earlier substages of pachytene in these autosomally synapsed Tex19.1 ^ −/− Spermatocytes. We also show that this skew towards earlier pachytene substages occurs in the absence of elevated Spermatocyte death in the population, that Spermatocytes with features of early pachytene are present in late stage Tex19.1 ^ −/− testis tubules and that the delay in histone H1t expression in response to loss of Tex19.1 does not occur in a Spo11 mutant background. Taken together, these data suggest that a recombination-dependent checkpoint may be able to modulate pachytene progression in mouse Spermatocytes to accommodate some types of recombination defect.
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Defects in meiotic recombination delay progression through pachytene in Tex19.1-/- mouse Spermatocytes.
Chromosoma, 2018Co-Authors: James H. Crichton, David Read, Ian R. AdamsAbstract:Recombination, synapsis, chromosome segregation and gene expression are co-ordinately regulated during meiosis to ensure successful execution of this specialised cell division. Studies with multiple mutant mouse lines have shown that mouse Spermatocytes possess quality control checkpoints that eliminate cells with persistent defects in chromosome synapsis. In addition, studies on Trip13mod/mod mice suggest that pachytene Spermatocytes that successfully complete chromosome synapsis can undergo meiotic arrest in response to defects in recombination. Here, we present additional support for a meiotic recombination-dependent checkpoint using a different mutant mouse line, Tex19.1-/-. The appearance of early recombination foci is delayed in Tex19.1-/- Spermatocytes during leptotene/zygotene, but some Tex19.1-/- Spermatocytes still successfully synapse their chromosomes and we show that these Spermatocytes are enriched for early recombination foci. Furthermore, we show that patterns of axis elongation, chromatin modifications and histone H1t expression are also all co-ordinately skewed towards earlier substages of pachytene in these autosomally synapsed Tex19.1-/- Spermatocytes. We also show that this skew towards earlier pachytene substages occurs in the absence of elevated Spermatocyte death in the population, that Spermatocytes with features of early pachytene are present in late stage Tex19.1-/- testis tubules and that the delay in histone H1t expression in response to loss of Tex19.1 does not occur in a Spo11 mutant background. Taken together, these data suggest that a recombination-dependent checkpoint may be able to modulate pachytene progression in mouse Spermatocytes to accommodate some types of recombination defect.
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Defects in Meiotic Recombination Delay Progression Through Pachytene in Mouse Spermatocytes
2017Co-Authors: James H. Crichton, David Read, Ian R. AdamsAbstract:During meiosis, recombination, synapsis, chromosome segregation and gene expression are co-ordinately regulated to ensure successful execution of this specialised cell division. In many model organisms, checkpoint controls can delay meiotic progression to allow defects or errors in these processes to be repaired or corrected. Mouse Spermatocytes possess quality control checkpoints that eliminate cells with persistent irreparable defects in chromosome synapsis or recombination, and here we show that a Spermatocyte checkpoint regulates progression through pachytene to accommodate delays in meiotic recombination. We have previously show that the appearance of early recombination foci is delayed in Tex19.1 -/- Spermatocytes during leptotene/zygotene, but some Tex19.1 -/- Spermatocytes still successfully synapse their chromosomes. Therefore, we have used autosomally synapsed Tex19.1 -/- mouse Spermatocytes to assess the consequences of delayed recombination on progression through pachytene. We show that these pachytene Spermatocytes are enriched for early recombination foci. This skew is not accompanied by cell death and likely reflects delays in the generation and/or maturation of recombination foci. Moreover, patterns of axis elongation, chromatin modifications, and histone H1t expression are also all skewed towards earlier substages of pachytene suggesting these events are co-ordinately regulated. Importantly, the delay in histone H1t expression in response to loss of Tex19.1 does not occur in a Spo11 mutant background, suggesting that histone H1t expression is being delayed by a recombination-dependent checkpoint. These data indicate that a recombination-dependent checkpoint operates in mouse Spermatocytes that can alter progression through pachytene to accommodate Spermatocytes with some types of recombination defect.
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Tex19.1 promotes Spo11-dependent meiotic recombination in mouse Spermatocytes - Fig 5
2017Co-Authors: James H. Crichton, David Read, Christopher J. Playfoot, Marie Maclennan, Howard J. Cooke, Ian R. AdamsAbstract:Tex19.1-/- Spermatocytes Have No Overt Defects in MEI4 Localisation or in H3K4me3 Accumulation at Recombination Hotspots. (A) Immunostaining of Spermatocyte chromosome spreads for the SC components SYCP3 (red) to identify leptotene nuclei and fragments of chromosome axes, and MEI4 (green). Scale bar 10 μm. (B) Quantification of MEI4 foci in leptotene Spermatocytes (218±12 for Tex19.1+/±, 223±10 for Tex19.1-/-, n = 48, 72 from three mice per genotype). Means are indicated with horizontal bars, ns indicates no significant difference (Mann-Whitney U test). (C) Immunostaining of Spermatocyte chromosome spreads for the SC components SYCP3 (red) and SYCE2 (blue) to identify leptotene nuclei, and H3K4me3 (green). Scale bar 10 μm. (D) Quantification of anti-H3K4me3 staining intensity (1648±202 and 1689±187 arbitrary units respectively, n = 21, 18 from three mice per genotype). Means are indicated with horizontal bars, ns indicates no significant difference (Mann-Whitney U test). (E, F) H3K4me3 chromatin immunoprecipitation (ChIP) from P16 Tex19.1+/± and Tex19.1-/- testes. qPCR for recombination hotspots (E) and retrotransposon sequences (F) was performed on H3K4me3 ChIP and abundance measured relative to input chromatin, then normalised to enrichment for the β-actin (Actb) transcriptional start site (TSS). Mean normalised enrichment ± standard error from three animals of each genotype is shown. Polr2a and Gapdh TSSs were used as positive controls, and an intragenic region of Polr2a as a negative control. ns indicates no significant difference, * indicates p
David Read - One of the best experts on this subject based on the ideXlab platform.
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Defects in meiotic recombination delay progression through pachytene in Tex19.1^−/− mouse Spermatocytes
Chromosoma, 2018Co-Authors: James H. Crichton, David Read, Ian R. AdamsAbstract:Recombination, synapsis, chromosome segregation and gene expression are co-ordinately regulated during meiosis to ensure successful execution of this specialised cell division. Studies with multiple mutant mouse lines have shown that mouse Spermatocytes possess quality control checkpoints that eliminate cells with persistent defects in chromosome synapsis. In addition, studies on Trip13 ^ mod/mod mice suggest that pachytene Spermatocytes that successfully complete chromosome synapsis can undergo meiotic arrest in response to defects in recombination. Here, we present additional support for a meiotic recombination-dependent checkpoint using a different mutant mouse line, Tex19.1 ^ −/− . The appearance of early recombination foci is delayed in Tex19.1 ^ −/− Spermatocytes during leptotene/zygotene, but some Tex19.1 ^ −/− Spermatocytes still successfully synapse their chromosomes and we show that these Spermatocytes are enriched for early recombination foci. Furthermore, we show that patterns of axis elongation, chromatin modifications and histone H1t expression are also all co-ordinately skewed towards earlier substages of pachytene in these autosomally synapsed Tex19.1 ^ −/− Spermatocytes. We also show that this skew towards earlier pachytene substages occurs in the absence of elevated Spermatocyte death in the population, that Spermatocytes with features of early pachytene are present in late stage Tex19.1 ^ −/− testis tubules and that the delay in histone H1t expression in response to loss of Tex19.1 does not occur in a Spo11 mutant background. Taken together, these data suggest that a recombination-dependent checkpoint may be able to modulate pachytene progression in mouse Spermatocytes to accommodate some types of recombination defect.
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Defects in meiotic recombination delay progression through pachytene in Tex19.1-/- mouse Spermatocytes.
Chromosoma, 2018Co-Authors: James H. Crichton, David Read, Ian R. AdamsAbstract:Recombination, synapsis, chromosome segregation and gene expression are co-ordinately regulated during meiosis to ensure successful execution of this specialised cell division. Studies with multiple mutant mouse lines have shown that mouse Spermatocytes possess quality control checkpoints that eliminate cells with persistent defects in chromosome synapsis. In addition, studies on Trip13mod/mod mice suggest that pachytene Spermatocytes that successfully complete chromosome synapsis can undergo meiotic arrest in response to defects in recombination. Here, we present additional support for a meiotic recombination-dependent checkpoint using a different mutant mouse line, Tex19.1-/-. The appearance of early recombination foci is delayed in Tex19.1-/- Spermatocytes during leptotene/zygotene, but some Tex19.1-/- Spermatocytes still successfully synapse their chromosomes and we show that these Spermatocytes are enriched for early recombination foci. Furthermore, we show that patterns of axis elongation, chromatin modifications and histone H1t expression are also all co-ordinately skewed towards earlier substages of pachytene in these autosomally synapsed Tex19.1-/- Spermatocytes. We also show that this skew towards earlier pachytene substages occurs in the absence of elevated Spermatocyte death in the population, that Spermatocytes with features of early pachytene are present in late stage Tex19.1-/- testis tubules and that the delay in histone H1t expression in response to loss of Tex19.1 does not occur in a Spo11 mutant background. Taken together, these data suggest that a recombination-dependent checkpoint may be able to modulate pachytene progression in mouse Spermatocytes to accommodate some types of recombination defect.
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Defects in Meiotic Recombination Delay Progression Through Pachytene in Mouse Spermatocytes
2017Co-Authors: James H. Crichton, David Read, Ian R. AdamsAbstract:During meiosis, recombination, synapsis, chromosome segregation and gene expression are co-ordinately regulated to ensure successful execution of this specialised cell division. In many model organisms, checkpoint controls can delay meiotic progression to allow defects or errors in these processes to be repaired or corrected. Mouse Spermatocytes possess quality control checkpoints that eliminate cells with persistent irreparable defects in chromosome synapsis or recombination, and here we show that a Spermatocyte checkpoint regulates progression through pachytene to accommodate delays in meiotic recombination. We have previously show that the appearance of early recombination foci is delayed in Tex19.1 -/- Spermatocytes during leptotene/zygotene, but some Tex19.1 -/- Spermatocytes still successfully synapse their chromosomes. Therefore, we have used autosomally synapsed Tex19.1 -/- mouse Spermatocytes to assess the consequences of delayed recombination on progression through pachytene. We show that these pachytene Spermatocytes are enriched for early recombination foci. This skew is not accompanied by cell death and likely reflects delays in the generation and/or maturation of recombination foci. Moreover, patterns of axis elongation, chromatin modifications, and histone H1t expression are also all skewed towards earlier substages of pachytene suggesting these events are co-ordinately regulated. Importantly, the delay in histone H1t expression in response to loss of Tex19.1 does not occur in a Spo11 mutant background, suggesting that histone H1t expression is being delayed by a recombination-dependent checkpoint. These data indicate that a recombination-dependent checkpoint operates in mouse Spermatocytes that can alter progression through pachytene to accommodate Spermatocytes with some types of recombination defect.
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Tex19.1 promotes Spo11-dependent meiotic recombination in mouse Spermatocytes - Fig 5
2017Co-Authors: James H. Crichton, David Read, Christopher J. Playfoot, Marie Maclennan, Howard J. Cooke, Ian R. AdamsAbstract:Tex19.1-/- Spermatocytes Have No Overt Defects in MEI4 Localisation or in H3K4me3 Accumulation at Recombination Hotspots. (A) Immunostaining of Spermatocyte chromosome spreads for the SC components SYCP3 (red) to identify leptotene nuclei and fragments of chromosome axes, and MEI4 (green). Scale bar 10 μm. (B) Quantification of MEI4 foci in leptotene Spermatocytes (218±12 for Tex19.1+/±, 223±10 for Tex19.1-/-, n = 48, 72 from three mice per genotype). Means are indicated with horizontal bars, ns indicates no significant difference (Mann-Whitney U test). (C) Immunostaining of Spermatocyte chromosome spreads for the SC components SYCP3 (red) and SYCE2 (blue) to identify leptotene nuclei, and H3K4me3 (green). Scale bar 10 μm. (D) Quantification of anti-H3K4me3 staining intensity (1648±202 and 1689±187 arbitrary units respectively, n = 21, 18 from three mice per genotype). Means are indicated with horizontal bars, ns indicates no significant difference (Mann-Whitney U test). (E, F) H3K4me3 chromatin immunoprecipitation (ChIP) from P16 Tex19.1+/± and Tex19.1-/- testes. qPCR for recombination hotspots (E) and retrotransposon sequences (F) was performed on H3K4me3 ChIP and abundance measured relative to input chromatin, then normalised to enrichment for the β-actin (Actb) transcriptional start site (TSS). Mean normalised enrichment ± standard error from three animals of each genotype is shown. Polr2a and Gapdh TSSs were used as positive controls, and an intragenic region of Polr2a as a negative control. ns indicates no significant difference, * indicates p
W Widlak - One of the best experts on this subject based on the ideXlab platform.
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heat shock transcription factor 1 down regulates Spermatocyte specific 70 kda heat shock protein expression prior to the induction of apoptosis in mouse testes
Genes to Cells, 2007Co-Authors: W Widlak, N Vydra, E Malusecka, Volha Dudaladava, Boleslaw Winiarski, Dorota ścieglinska, P WidlakAbstract:Expression of constitutively active heat shock transcription factor 1 (HSF1) in mouse Spermatocytes induces apoptosis and leads to male infertility. We report here that prior to the onset of massive apoptosis caused by expression of active HSF1 in Spermatocytes a marked reduction in Spermatocyte-specific Hsp70.2 mRNA and protein levels occurs. In addition, HSP70.2 protein relocalizes from a predominant cytoplasmic to a nuclear position in developing Spermatocytes that express active HSF1. Later in the developmental stages, cells undergoing HSF1-induced apoptosis essentially lack the HSP70.2 protein. The down-regulation of Hsp70.2 gene expression by HSF1 is paradoxical because HSF1 is the prototypical activator of HSP genes. Furthermore, HSF1-mediated repression neither involved a heat shock element (HSE)-like sequence adjacent to the Hsp70.2 gene nor were Hsp70.2 promoter sequences associated directly with HSF1. Interestingly, other Spermatocyte- and spermatid-specific transcripts are also down-regulated in testes of transgenic mice expressing active HSF1, suggesting involvement of a putative HSF1-dependent block of development of spermatogenic cells. Importantly however, transcription of the Hsp70.2 gene is down-regulated in testes of wild-type mice subjected to a hyperthermia that induces transient activation of HSF1, indicating that the Spermatocyte-specific activity of HSF1 might misdirect a network of transcription factors required for proper regulation of Hsp70.2.
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Spermatocyte-specific expression of constitutively active heat shock factor 1 induces HSP70i-resistant apoptosis in male germ cells
Cell Death & Differentiation, 2006Co-Authors: N Vydra, E Malusecka, M Jarzab, K Lisowska, M Glowala-kosinska, K Benedyk, P Widlak, Z Krawczyk, W WidlakAbstract:Spermatocytes, the most sensitive male germ cells to heat-induced apoptosis, do not respond to hyperthermia by inducing heat shock proteins (HSPs), including HSP70i, which has been previously shown to confer resistance to apoptosis in somatic cells. To dissect the mechanism of heat-induced apoptosis and to determine if we could protect Spermatocytes by expressing HSP70i, we engineered transgenic mice that express in Spermatocytes constitutively active h eat s hock transcription f actor (HSF)1. Such HSF1 expression did not lead to transcription of inducible Hsp70 genes, but instead induced caspase-dependent apoptosis that mimicked heat shock-induced death of spermatogenic cells. Both mitochondria-dependent and death receptor-dependent pathways appear to be involved in such HSF1-induced apoptosis: the levels of Bcl-2 family proteins became increased, p53 protein accumulated and expression levels of caspase-8 and death-receptor-interacting proteins (including F as- a ssociated d eath d omain protein and T NF r eceptor a ssociated d eath d omain protein) became elevated. Surprisingly, the constitutive Spermatocyte-specific expression of HSP70i in double-transgenic males did not protect against such HSF1-induced apoptosis.
Geert Hamer - One of the best experts on this subject based on the ideXlab platform.
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distinct prophase arrest mechanisms in human male meiosis
Development, 2018Co-Authors: Sabrina Z Jan, Aldo Jongejan, Cindy M Korver, Saskia K M Van Daalen, Ans M M Van Pelt, Sjoerd Repping, Geert HamerAbstract:To prevent chromosomal aberrations being transmitted to the offspring, strict meiotic checkpoints are in place to remove aberrant Spermatocytes. However, in about 1% of males these checkpoints cause complete meiotic arrest leading to azoospermia and subsequent infertility. Here, we unravel two clearly distinct meiotic arrest mechanisms that occur during prophase of human male meiosis. Type I arrested Spermatocytes display severe asynapsis of the homologous chromosomes, disturbed XY-body formation and increased expression of the Y chromosome-encoded gene ZFY and seem to activate a DNA damage pathway leading to induction of p63, possibly causing Spermatocyte apoptosis. Type II arrested Spermatocytes display normal chromosome synapsis, normal XY-body morphology and meiotic crossover formation but have a lowered expression of several cell cycle regulating genes and fail to silence the X chromosome-encoded gene ZFX. Discovery and understanding of these meiotic arrest mechanisms increases our knowledge of how genomic stability is guarded during human germ cell development.
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distinct prophase arrest mechanisms in human male meiosis
bioRxiv, 2017Co-Authors: Sabrina Z Jan, Aldo Jongejan, Cindy M Korver, Saskia K M Van Daalen, Ans M M Van Pelt, Sjoerd Repping, Geert HamerAbstract:To prevent chromosomal aberrations to be transmitted to the offspring, strict meiotic checkpoints are in place to remove aberrant Spermatocytes. However, in about 1% of all males these checkpoints cause complete meiotic arrest leading to azoospermia and subsequent infertility. We here unravel two clearly distinct meiotic arrest mechanisms that act during the prophase of human male meiosis. Type I arrested Spermatocytes display severe asynapsis of the homologous chromosomes, disturbed XY-body formation and increased expression of the Y-chromosome encoded gene ZFY and seem to activate a DNA damage pathway leading to induction of p63 mediated Spermatocyte elimination. Type II arrested Spermatocytes display normal chromosome synapsis, normal XY-body morphology and meiotic crossover formation but have a lowered expression of several cell cycle regulating genes and fail to properly silence the X-chromosome encoded gene ZFX. Discovery and understanding of these meiotic arrest mechanisms increases our knowledge on how genomic stability is guarded during human germ cell development.
