The Experts below are selected from a list of 264 Experts worldwide ranked by ideXlab platform
Peter B. Moens - One of the best experts on this subject based on the ideXlab platform.
-
Mutant meiotic chromosome core components in mice can cause apparent sexual dimorphic endpoints at prophase or X–Y defective male-specific sterility
Chromosoma, 2005Co-Authors: Nadine K Kolas, Edyta Marcon, Michael A Crackower, Christer Hoog, Joseph M. Penninger, Barbara Spyropoulos, Peter B. MoensAbstract:Genetic modifications causing germ cell death during meiotic prophase in the mouse frequently have sexually dimorphic phenotypes where oocytes reach more advanced stages than Spermatocytes. To determine to what extent these dimorphisms are due to differences in male versus female meiotic prophase development, we compared meiotic chromosome events in the two sexes in both wild-type and mutant mice. We report the abundance and time course of appearance of structural and recombination-related proteins of fetal oocyte nuclei. Oocytes at successive days post coitus show rapid, synchronous meiotic prophase development compared with the continuous spermatocyte development in adult testis. Consequently, a genetic defect requiring 2–3 days from the onset of prophase to reach arrest registers pachytene as the developmental endpoint in oocytes. Pachytene Spermatocytes, on the other hand, which normally accumulate during days 4–10 after the onset of prophase, will be rare, giving the appearance of an earlier endpoint than in oocytes. We conclude that these different logistics create apparent sexually dimorphic endpoints. For more pronounced sexual dimorphisms, we examined meiotic prophase of mice with genetic modifications of meiotic chromosome core components that cause male but not female sterility. The correlations between male sterility and alterations in the organization of the sex chromosome cores and X–Y chromatin may indicate that impaired signals from the XY domain (XY chromosome cores, chromatin, dense body and sex body) may interfere with the progression of the spermatocyte through prophase. Oocytes, in the absence of the X–Y pair, do not suffer such defects.
-
mutant meiotic chromosome core components in mice can cause apparent sexual dimorphic endpoints at prophase or x y defective male specific sterility
Chromosoma, 2005Co-Authors: Nadine K Kolas, Edyta Marcon, Michael A Crackower, Christer Hoog, Joseph M. Penninger, Barbara Spyropoulos, Peter B. MoensAbstract:Genetic modifications causing germ cell death during meiotic prophase in the mouse frequently have sexually dimorphic phenotypes where oocytes reach more advanced stages than Spermatocytes. To determine to what extent these dimorphisms are due to differences in male versus female meiotic prophase development, we compared meiotic chromosome events in the two sexes in both wild-type and mutant mice. We report the abundance and time course of appearance of structural and recombination-related proteins of fetal oocyte nuclei. Oocytes at successive days post coitus show rapid, synchronous meiotic prophase development compared with the continuous spermatocyte development in adult testis. Consequently, a genetic defect requiring 2–3 days from the onset of prophase to reach arrest registers pachytene as the developmental endpoint in oocytes. Pachytene Spermatocytes, on the other hand, which normally accumulate during days 4–10 after the onset of prophase, will be rare, giving the appearance of an earlier endpoint than in oocytes. We conclude that these different logistics create apparent sexually dimorphic endpoints. For more pronounced sexual dimorphisms, we examined meiotic prophase of mice with genetic modifications of meiotic chromosome core components that cause male but not female sterility. The correlations between male sterility and alterations in the organization of the sex chromosome cores and X–Y chromatin may indicate that impaired signals from the XY domain (XY chromosome cores, chromatin, dense body and sex body) may interfere with the progression of the spermatocyte through prophase. Oocytes, in the absence of the X–Y pair, do not suffer such defects.
-
atm deficiency results in severe meiotic disruption as early as leptonema of prophase i
Development, 1998Co-Authors: Carrolee Barlow, Peter B. Moens, Marek Liyanage, Madalina Tarsounas, Kunio Nagashima, Kevin K Brown, Scott T Rottinghaus, Stephen P Jackson, Danilo A Tagle, Thomas RiedAbstract:Infertility is a common feature of the human disorder ataxia-telangiectasia and Atm-deficient mice are completely infertile. To gain further insight into the role of ATM in meiosis, we examined meiotic cells in Atm-deficient mice during development. Spermatocyte degeneration begins between postnatal days 8 and 16.5, soon after entry into prophase I of meiosis, while oocytes degenerate late in embryogenesis prior to dictyate arrest. Using electron microscopy and immunolocalization of meiotic proteins in mutant adult Spermatocytes, we found that male and female gametogenesis is severely disrupted in Atm-deficient mice as early as leptonema of prophase I, resulting in apoptotic degeneration. A small number of mutant cells progress into later stages of meiosis, but no cells proceed beyond prophase I. ATR, a protein related to ATM, DMC1, a RAD51 family member, and RAD51 are mislocalized to chromatin and have reduced localization to developing synaptonemal complexes in Spermatocytes from Atm-deficient mice, suggesting dysregulation of the orderly progression of meiotic events. ATM protein is normally present at high levels primarily in ova cytoplasm of developing ovarian follicles, and in the nucleus of spermatogonia and to a lesser extent in spermatoctyes, but without localization to the synaptonemal complex. We propose a model in which ATM acts to monitor meiosis by participation in the regulation or surveillance of meiotic progression, similar to its role as a monitor of mitotic cell cycle progression.
Ian R. Adams - One of the best experts on this subject based on the ideXlab platform.
-
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.
-
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.
-
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.
Christer Hoog - One of the best experts on this subject based on the ideXlab platform.
-
Mutant meiotic chromosome core components in mice can cause apparent sexual dimorphic endpoints at prophase or X–Y defective male-specific sterility
Chromosoma, 2005Co-Authors: Nadine K Kolas, Edyta Marcon, Michael A Crackower, Christer Hoog, Joseph M. Penninger, Barbara Spyropoulos, Peter B. MoensAbstract:Genetic modifications causing germ cell death during meiotic prophase in the mouse frequently have sexually dimorphic phenotypes where oocytes reach more advanced stages than Spermatocytes. To determine to what extent these dimorphisms are due to differences in male versus female meiotic prophase development, we compared meiotic chromosome events in the two sexes in both wild-type and mutant mice. We report the abundance and time course of appearance of structural and recombination-related proteins of fetal oocyte nuclei. Oocytes at successive days post coitus show rapid, synchronous meiotic prophase development compared with the continuous spermatocyte development in adult testis. Consequently, a genetic defect requiring 2–3 days from the onset of prophase to reach arrest registers pachytene as the developmental endpoint in oocytes. Pachytene Spermatocytes, on the other hand, which normally accumulate during days 4–10 after the onset of prophase, will be rare, giving the appearance of an earlier endpoint than in oocytes. We conclude that these different logistics create apparent sexually dimorphic endpoints. For more pronounced sexual dimorphisms, we examined meiotic prophase of mice with genetic modifications of meiotic chromosome core components that cause male but not female sterility. The correlations between male sterility and alterations in the organization of the sex chromosome cores and X–Y chromatin may indicate that impaired signals from the XY domain (XY chromosome cores, chromatin, dense body and sex body) may interfere with the progression of the spermatocyte through prophase. Oocytes, in the absence of the X–Y pair, do not suffer such defects.
-
mutant meiotic chromosome core components in mice can cause apparent sexual dimorphic endpoints at prophase or x y defective male specific sterility
Chromosoma, 2005Co-Authors: Nadine K Kolas, Edyta Marcon, Michael A Crackower, Christer Hoog, Joseph M. Penninger, Barbara Spyropoulos, Peter B. MoensAbstract:Genetic modifications causing germ cell death during meiotic prophase in the mouse frequently have sexually dimorphic phenotypes where oocytes reach more advanced stages than Spermatocytes. To determine to what extent these dimorphisms are due to differences in male versus female meiotic prophase development, we compared meiotic chromosome events in the two sexes in both wild-type and mutant mice. We report the abundance and time course of appearance of structural and recombination-related proteins of fetal oocyte nuclei. Oocytes at successive days post coitus show rapid, synchronous meiotic prophase development compared with the continuous spermatocyte development in adult testis. Consequently, a genetic defect requiring 2–3 days from the onset of prophase to reach arrest registers pachytene as the developmental endpoint in oocytes. Pachytene Spermatocytes, on the other hand, which normally accumulate during days 4–10 after the onset of prophase, will be rare, giving the appearance of an earlier endpoint than in oocytes. We conclude that these different logistics create apparent sexually dimorphic endpoints. For more pronounced sexual dimorphisms, we examined meiotic prophase of mice with genetic modifications of meiotic chromosome core components that cause male but not female sterility. The correlations between male sterility and alterations in the organization of the sex chromosome cores and X–Y chromatin may indicate that impaired signals from the XY domain (XY chromosome cores, chromatin, dense body and sex body) may interfere with the progression of the spermatocyte through prophase. Oocytes, in the absence of the X–Y pair, do not suffer such defects.
-
Telomere Attachment, Meiotic Chromosome Condensation, Pairing, and Bouquet Stage Duration Are Modified in Spermatocytes Lacking Axial Elements
Molecular biology of the cell, 2003Co-Authors: Bodo Liebe, Manfred Alsheimer, Christer Hoog, Ricardo Benavente, Harry ScherthanAbstract:During the extended prophase to the meiosis I division, chromosomes assemble axial elements (AE) along replicated sister chromatids whose ends attach to the inner nuclear membrane (NM) via a specialized conical thickening. Here, we show at the EM level that in Sycp3 - / - spermatocyte chromosomes lack the AE and the conical end thickening, but still they attach their telomeres to the inner NM with an electron-dense plate that contains T 2 AG 3 repeats. Immunofluorescence detected telomere proteins, SCP2, and the meiosis-specific cohesin STAG3 at the sycp3 - / - telomere. Bouquet stage Spermatocytes were approximately threefold enriched, and the number of telomere but not centromere signals was reduced to the haploid in advanced sycp3 - / - Spermatocytes, which indicates a special mode of homolog pairing at the mammalian telomere. Fluorescence in situ hybridization with mouse chromosome 8- and 12-specific subsatellite probes uncovered reduced levels of regional homolog pairing, whereas painting of chromosomes 13 revealed partial or complete juxtapositioning of homologs; however, condensation of Sycp3 - / - bivalents was defective. Electron microscopic analysis of AE-deficient Spermatocytes revealed that transverse filaments formed short structures reminiscent of the synaptonemal complex central region, which likely mediate stable homolog pairing. It appears that the AE is required for chromosome condensation, rapid exit from the bouquet stage, and fine-tuning of homolog pairing.
Nadine K Kolas - One of the best experts on this subject based on the ideXlab platform.
-
Mutant meiotic chromosome core components in mice can cause apparent sexual dimorphic endpoints at prophase or X–Y defective male-specific sterility
Chromosoma, 2005Co-Authors: Nadine K Kolas, Edyta Marcon, Michael A Crackower, Christer Hoog, Joseph M. Penninger, Barbara Spyropoulos, Peter B. MoensAbstract:Genetic modifications causing germ cell death during meiotic prophase in the mouse frequently have sexually dimorphic phenotypes where oocytes reach more advanced stages than Spermatocytes. To determine to what extent these dimorphisms are due to differences in male versus female meiotic prophase development, we compared meiotic chromosome events in the two sexes in both wild-type and mutant mice. We report the abundance and time course of appearance of structural and recombination-related proteins of fetal oocyte nuclei. Oocytes at successive days post coitus show rapid, synchronous meiotic prophase development compared with the continuous spermatocyte development in adult testis. Consequently, a genetic defect requiring 2–3 days from the onset of prophase to reach arrest registers pachytene as the developmental endpoint in oocytes. Pachytene Spermatocytes, on the other hand, which normally accumulate during days 4–10 after the onset of prophase, will be rare, giving the appearance of an earlier endpoint than in oocytes. We conclude that these different logistics create apparent sexually dimorphic endpoints. For more pronounced sexual dimorphisms, we examined meiotic prophase of mice with genetic modifications of meiotic chromosome core components that cause male but not female sterility. The correlations between male sterility and alterations in the organization of the sex chromosome cores and X–Y chromatin may indicate that impaired signals from the XY domain (XY chromosome cores, chromatin, dense body and sex body) may interfere with the progression of the spermatocyte through prophase. Oocytes, in the absence of the X–Y pair, do not suffer such defects.
-
mutant meiotic chromosome core components in mice can cause apparent sexual dimorphic endpoints at prophase or x y defective male specific sterility
Chromosoma, 2005Co-Authors: Nadine K Kolas, Edyta Marcon, Michael A Crackower, Christer Hoog, Joseph M. Penninger, Barbara Spyropoulos, Peter B. MoensAbstract:Genetic modifications causing germ cell death during meiotic prophase in the mouse frequently have sexually dimorphic phenotypes where oocytes reach more advanced stages than Spermatocytes. To determine to what extent these dimorphisms are due to differences in male versus female meiotic prophase development, we compared meiotic chromosome events in the two sexes in both wild-type and mutant mice. We report the abundance and time course of appearance of structural and recombination-related proteins of fetal oocyte nuclei. Oocytes at successive days post coitus show rapid, synchronous meiotic prophase development compared with the continuous spermatocyte development in adult testis. Consequently, a genetic defect requiring 2–3 days from the onset of prophase to reach arrest registers pachytene as the developmental endpoint in oocytes. Pachytene Spermatocytes, on the other hand, which normally accumulate during days 4–10 after the onset of prophase, will be rare, giving the appearance of an earlier endpoint than in oocytes. We conclude that these different logistics create apparent sexually dimorphic endpoints. For more pronounced sexual dimorphisms, we examined meiotic prophase of mice with genetic modifications of meiotic chromosome core components that cause male but not female sterility. The correlations between male sterility and alterations in the organization of the sex chromosome cores and X–Y chromatin may indicate that impaired signals from the XY domain (XY chromosome cores, chromatin, dense body and sex body) may interfere with the progression of the spermatocyte through prophase. Oocytes, in the absence of the X–Y pair, do not suffer such defects.
Mary Ann Handel - One of the best experts on this subject based on the ideXlab platform.
-
Spermatocyte responses in vitro to induced DNA damage
Molecular reproduction and development, 2006Co-Authors: Shannon Matulis, Mary Ann HandelAbstract:Spermatocytes normally sustain many meiotically induced double-strand DNA breaks (DSBs) early in meiotic prophase; in autosomal chromatin, these are repaired by initiation of meiotic homologous-recombination processes. Little is known about how Spermatocytes respond to environmentally induced DNA damage after recombination-related DSBs have been repaired. The experiments described here tested the hypothesis that, even though actively completing meiotic recombination, pachytene Spermatocytes cultured in the absence of testicular somatic cells initiate appropriate chromatin remodeling and cell-cycle responses to environmentally induced DNA damage. Two DNA-damaging agents were employed for in vitro treatment of pachytene Spermatocytes: γ-irradiation and etoposide, a topoisomerase II (TOP2) inhibitor that results in persistent unligated DSBs. Chromatin modifications associated with DSBs were monitored after exposure by labeling surface-spread chromatin with antibodies against RAD51 (which recognizes DSBs) and the phosphorylated variant of histone H2AFX (herein designated by its commonly used symbol, H2AX), γH2AX (which modifies chromatin associated with DSBs). Both γH2AX and RAD51 were rapidly recruited to irradiation- or etoposide-damaged chromatin. These chromatin modifications imply that Spermatocytes recruit active DNA damage responses, even after recombination is substantially completed. Furthermore, irradiation-induced DNA damage inhibited okadaic acid-induced progression of Spermatocytes from meiotic prophase to metaphase I (MI), implying efficacy of DNA damage checkpoint mechanisms. Apoptotic responses of Spermatocytes with DNA damage differed, with an increase in frequency of early apoptotic Spermatocytes after etoposide treatment, but not following irradiation. Taken together, these results demonstrate modification of pachytene spermatocyte chromatin and inhibition of meiotic progress after DNA damage by mechanisms that may ensure gametic genetic integrity. Mol. Reprod. Dev. 1061–1072, 2006. © 2006 Wiley-Liss, Inc.
-
Factors Affecting Meiotic and Developmental Competence of Primary Spermatocyte Nuclei Injected into Mouse Oocytes
Biology of reproduction, 1998Co-Authors: Yasuyuki Kimura, Hiroyuki Tateno, Mary Ann Handel, Ryuzo YanagimachiAbstract:Mature mouse oocytes that have received the nuclei of pachytene primary Spermatocytes (or metaphase I chromosomes of primary Spermatocytes) can develop into fertile offspring. However, success rate in this study was low. No more than 3.8% of transferred 2-cell embryos arising from spermatocyte-injected oocytes developed to full term. Nevertheless, the birth of normal offspring seems to suggest that at least in some primary Spermatocytes the functional genomic imprinting is complete before transfer and/or consolidated after the transfer. Although injected spermatocyte nuclei could undergo two successive meiotic divisions within oocytes, abnormalities of both divisions were commonly observed, and sister chromatids often separated prematurely during the second meiotic division. Chromosome breakage/rearrangements were also frequently seen before the first cleavage. Such abnormalities of chromosome behavior are probably the major causes of the poor preimplantation development of zygotes arising from primary spermatocyte-injected oocytes. Thus, clinical use of primary Spermatocytes as substitutes for spermatozoa in assisted fertilization is not advisable until the causes of chromosomal abnormalities are better understood through extensive animal studies.
-
induced premature g2 m phase transition in pachytene Spermatocytes includes events unique to meiosis
Developmental Biology, 1995Co-Authors: Tim Wiltshire, Cynthia Park, Kim A Caldwell, Mary Ann HandelAbstract:Abstract Little is known about the control of events ending the lengthy prophase of meiosis I and leading to the G2/M-phase transition in mammalian Spermatocytes, primarily because the relevant late pachytene, diplotene, and MI cells are present in low numbers in the testis and it is not possible to isolate them in significant numbers. We have utilized short-term cultures of pachytene Spermatocytes from the mouse to study events of the G2/M cell-cycle transition induced by the protein phosphatase inhibitor okadaic acid (OA). Treatment of cultured pachytene Spermatocytes with OA induced a rapid and premature onset of events leading to the M phase, visualized cytologically by nuclear envelope breakdown and chromosome condensation. After OA treatment, condensed chromosomes were seen as bivalents, not as univalents. Treatment with OA induced disassembly of synaptonemal complexes and resolution of crossovers as cytologically visible chiasmata. Chiasmata counts were similar in treated cells and control cells. Thus, surprisingly, even though the treated cells were in the pachytene substage of meiotic prophase, events of recombination were apparently completed to the point of chiasma formation in the majority of these cells. The sex chromosomes, forming the sex body of the pachytene spermatocyte, lagged behind the autosomal chromosomes in their condensation and progression toward the M phase. Treatment with OA induced an increase in histone HI kinase activity, generally used as an indicator of metaphase-promoting factor (MPF) activity; furthermore, the OA-induced cell-cycle transition does not require new protein synthesis. These results suggest that OA treatment overrides a cell-cycle checkpoint control that normally keeps pachytene Spermatocytes in a lengthy prophase and that this control may be exerted by regulation of protein phosphorylation status.
