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1.
The clastogenic effect of the anticancer drug cis-diamminedichloroplatinum (II) (cisplatin) on meiotic prophase in primary spermatocytes and on spermatogonial stem cells of male (101/E1 x C3H/E1)F1 mice was studied. The intraperitoneal doses of cisplatin tested were 5.0, 7.5 and 10.0 mg/kg. Chromosomal aberrations were examined at diakinesis-metaphase 1 of meiosis 1-13 days after treatment, representing cells treated at diplotene, pachytene, zygotene, leptotene an preleptotene. Reciprocal translocations were evaluated 63-70 days after treatment, representing treated stem-cell spermatogonia. Cisplatin had a toxic effect in zygotene to preleptotene of meiosis, as indicated by the significant reduction in testicular weight. At diplotene, pachytene and zygotene no enhancement of aberrations was found. An increase in aberrant cells was observed during leptotene with preleptotene being the most sensitive stage. The dose-response relationship for aberrant cells was linear on day 13 after treatment. It is concluded that, like mitomycin C (Adler, 1976), cisplatin primarily caused aberrations during the premeiotic phase of DNA synthesis. No significant increase of translocation multivalents was found after treatment of stem-cell spermatogonia. 相似文献
2.
《Mutation Research Letters》1990,243(3):173-178
The clastogenic effect of the anticancer drug cis-diamminedichloroplatinum(II) (cisplatin) on meiotic prophase in primary spermatocytes and on spermatologonial stem cells of male (101/E1 × C3H/E1)F1 mice was studied. The intraperitoneal doses of cisplatin tested were 5.0, 7.5 and 10.0 mg/kg. Chromosomal aberrations were examined at diakinesis-metaphase 1 of meiosis 1–13 days after treatment, representing cells treated at diplotene, pachytene, zygotene, leptotene an preleptotene. Reciprocal translocations were evaluated 63–70 days after treatment, representing treated stem-cell spermatogonia.Cisplatin had a toxic effect in zygotene to preleptotene of meiosis, as indicated by the significant reduction in testicular weight. At diplotene, pachytene and zygotene no enhancement of aberrations was found. An increase in aberrant cells was observed during leptotene with preleptotene being the most sensitive stage. The dose-response relationship for aberrant cells was linear on day 13 after treatment. It is concluded that, like mitomycin C (Alder, 1976), cisplatin primarily caused aberrations during the premeiotic phase of DNA synthesis. No significant increase of translocation multivalents was found after treatment of stem-cell spermatogonia. 相似文献
3.
Thirty adult stallion testes were selected with high (n = 15) and low (n = 15) Daily Sperm Production (DSP)/testis. Parenchymal samples were prepared for morphometric analysis, and the numbers of germ cells and Sertoli cells were determined. Testicular samples were homogenized, and germ cells and Sertoli cells were enumerated using phase contrast microscopy. Numbers of germ cells and Sertoli cells and potential DSP during spermatogenesis were determined. Significant correlations existed between morphometric and homogenate determinations of number per testis of preleptotene, leptotene plus zygotene primary spermatocytes (r = 0.58; P < 0.001), pachytene plus diplotene primary spermatocytes (r = 0.67; P < 0.0001), all primary spermatocytes (r = 0.67; P < 0.0001), round spermatids (r = 0.72; P < 0.0001), and Sertoli cells (r = 0.70; P < 0.0001). Significant correlations (P < 0.0001) existed between morphometric and homogenate determination of DSP/testis based on preleptotene, leptotene plus zygotene primary spermatocytes (r = 0.78), pachytene plus diplotene primary spermatocytes (r = 0.88), and round spermatids (r = 0.85). Using morphometric determination as the standard, the sensitivity (i.e., ability to detect low DSP/testis) and specificity (i.e., ability to detect high DSP/testis) by homogenate enumeration of germ cells was 81 and 93% for round spermatids, 100 and 24% for pachytene plus diplotene primary spermatocytes, and 67 and 87% for preleptotene, leptotene plus zygotene primary spermatocytes, respectively. Enumeration of primary spermatocytes in homogenates was less accurate than enumeration of round or elongated spermatids. Enumeration of round and elongated spermatids in homogenates was a rapid and useful method for determining DSP in horses, and it may prove to be a useful technique for quantitating potential DSP from testicular biopsies. 相似文献
4.
The process of homolog pairing is well characterised in meiosis of male mammals, but much less information is available from female meiosis. We have therefore studied telomere dynamics by FISH and synapsis formation by immunostaining of synaptonemal complex proteins (SCP3, SCP1) on ovarian sections from 15 bovine fetuses, which covered the entire female prophase I. Telomeres displayed a dispersed intranuclear distribution in oogonia and relocated to the nuclear periphery during the preleptotene stage. Tight telomere clustering (bouquet formation) coincided with synapsis initiation at the leptotene/zygotene transition. Clustering of telomeres persisted during zygotene and even into the pachytene stage in a subset of nuclei, while it was absent in diplotene/dictyotene stage nuclei. Thus, the bouquet stage in the bovine female lasts significantly longer than in the male. Further, we observed that synapsis in the female initiated both terminally and interstitially in earliest zygotene stage oocytes, which contrasts with the predominantly terminal synapsis initiation in early zygotene spermatocytes of the bovine male. Altogether, our data disclose a sex-specific difference in telomere dynamics and synapsis initiation patterns in male and female bovine germ cells that may be related to the sex-specific differences in recombination rates observed in this and other mammalian species. 相似文献
5.
Biochemical analysis of the male germ cell-associated kinase (mak) gene, which was isolated recently by using weak cross-hybridization with the v-ros tyrosine kinase gene, revealed that the gene was highly expressed in mammalian testicular germ cells, but not in ovarian cells. In order to identify the cells which express the mak gene in more detail, we localized mak mRNA in frozen sections of mouse testis by non-radioactive in situ hybridization. In this study, we utilized thymine-thymine (T-T) dimerized mak cDNA as a haptenic, non-radioactive probe, and the signal was detected enzyme-immunohistochemically by using an anti-T-T antibody. As a result, mak mRNA was localized intensely in late pachytene (stage X) and diplotene (stage XI) spermatocytes, and faintly in dividing spermatocytes (stage XII) and early round spermatids (stage I-II), suggesting that the gene may play an important role in the phase around meiotic cell division, but not throughout the entire meiosis. 相似文献
6.
A light microscopic study of the development and behaviour of the synaptonemal complex in spermatocytes of the mouse 总被引:2,自引:0,他引:2
A method is presented for the sequential analysis of male meiosis using hydroxyurea (HU). HU produces a gap in the spermatogenic line. The front of surviving cells behind the gap was examined day by day using silverstained whole mount spreads on glass slides. With this method it was possible to study the development and behaviour of the synaptonemal complex (SC) in mouse spermatocytes by the light microscope. At zygotene no unpaired axial elements could be seen. Unpaired axial elements were found to be specific for the diplotene stage. The axes of the XY pair could be recognized from late zygotene up to diplotene. 相似文献
7.
A method is presented for sequential analysis of the development and behaviour of the Synaptonemal Complex (SC) in primary spermatocytes of male mice, using agar filtration for electron microscope grid preparation. The mice were treated with hydroxyurea (HU) to produce a gap in the spermatogenic line. The front of surviving cells behind the gap was examined day by day. The first visible parts of unpaired axial elements, with some barely recognizable paired regions were found 9 days after the last HU injection i.e. directly after the last S-phase before meiosis. During mid zygotene and late zygotene the axes of the autosomes had a fuzzy ill-defined appearance with irregular regions of apparent thickening. The axes of the XY pair could be recognized only at late zygotene. During pachytene the SCs of the autosomal pairs did not show a significant change except for a slight increase in size of the attachment points of the axial elements. On the first day of pachytene the axes of the XY pair appeared thin and long. On the second day the axes of the XY pair showed maximal pairing of about 50% of the axis of the Y chromosome. From the third to the fifth day a decrease of the paired region of the sex chromosomes was found together with an increase in thickness of the axes, which reached its maximum on the fourth day. Diplotene could be easily recognized: the autosomal axes showed a sharp, well-defined outline with thick attachment points with deltoid structure, and desynapsis was very clear. The axes of the XY pair showed variation during diplotene but on the third day of diplotene a characteristic bulging could be seen. The axes of the autosomes disappeared at this time and in most cases only the attachment points remained visible. The duration of the prophase classes of meiosis I was found to be: zygotene approximately 2 days; pachytene a little more than 5 days and diplotene approximately 3 days. Leptotene could not be traced by the method used. If it exists at all, it must be a stage of very short duration. 相似文献
8.
Hasbaira Bolor Wei Dong Zhao Akira Ishikawa Noboru Wakasugi 《Experimental Animals》2005,54(4):327-337
A spontaneous mutant having small testes was found in a laboratory mouse strain of mixed origins. The testis size was 1/3-1/2 of normal size, but no significant difference was seen in body mass and weight of organs such as kidney and seminal vesicle, which are influenced by androgen. Small testis males were found to be infertile by the mating test, although formation of a vaginal plug was normally observed in their female partners. Histological and air-dried specimens revealed degeneration of zygotene or early pachytene spermatocytes and very few numbers of pachytene and diplotene spermatocytes, round and elongate spermatids and mature spermatozoa in the mutant testis. Therefore, it was concluded that spermatogenesis is disrupted at the zygotene to early pachytene stages of meiosis in the mutant males. Segregation ratios of normal and mutant males were in accord with the assumption that the small testis character is caused by an autosomal recessive mutation. This mutant may be useful for research that would contribute to the elucidation of genetic mechanisms controlling the process of spermatogenesis and as a model animal for male infertility in humans. 相似文献
9.
Synaptonemal complexes in a subfertile man with a pericentric inversion in chromosome 21. Heterosynapsis without previous homosynapsis 总被引:6,自引:0,他引:6
O Gabriel-Robez C Ratomponirina M Croquette J Couturier Y Rumpler 《Cytogenetics and cell genetics》1988,48(2):84-87
Analysis of surface-spread synaptonemal complexes of zygotene and pachytene spermatocytes was carried out on a human male carrier of a pericentric inversion of chromosome 21 ascertained after four miscarriages. The synaptic behavior of the bivalent, which could be unambiguously identified by its nonaligned kinetochores, was analyzed. All zygotene and pachytene spermatocytes had 22 linearly paired autosomal bivalents, with apparently normal synaptonemal complexes, and no evidence of a loop configuration in the 50 cells analyzed. According to the XY type (classification of Solari), the cells were distributed across zygotene and pachytene stages, not exclusively in the late pachytene to which adjustment is conventionally thought to be confined. It is suggested that inverted segments heterosynapse at early pachytene, without previous homosynapsis. It is expected that this meiotic process leads to failure of crossing-over, reduces the production of unbalanced gametes, and the risk of recombinant offspring, but can increase the incidence of aneuploidy as a result of nondisjunction during meiosis I (a frequent cause of pregnancy wastage). 相似文献
10.
Stage-specific protein synthesis by isolated spermatogenic cells throughout meiosis and early spermiogenesis in the mouse 总被引:4,自引:0,他引:4
D A O'Brien 《Biology of reproduction》1987,37(1):147-157
Spermatogenic cells isolated from prepubertal and adult mice by unit gravity sedimentation have been used to examine proteins synthesized in a stage-specific manner throughout meiosis and early spermiogenesis. Preleptotene, leptotene/zygotene, and pachytene spermatocytes were isolated from 17-day-old mice. Adult pachytene spermatocytes and round spermatids were isolated from mature animals. These germ cells were then cultured in defined medium with [35S]methionine [( 35S]met) for 4-5 h. For each cell type, relative [35S]met incorporation was determined and labeled proteins were compared by two-dimensional (2D) polyacrylamide gel electrophoresis and autoradiography. Levels of [35S]met incorporation by isolated germ cells correlate closely with previous autoradiographic estimates of protein synthesis during spermatogenesis (Monesi, 1967). Pachytene spermatocytes from prepubertal mice incorporate the highest levels of [35S]met, when expressed either as cpm/-10(6) cells or cpm/mg protein. Comparisons of 2D autoradiograms indicated that many proteins, including actin and tubulins, are synthesized at approximately equal levels in all stages examined. Other proteins, including heat-shock proteins and multiple plasma membrane constituents, are synthesized in a stage-specific manner in leptotene/zygotene spermatocytes, pachytene spermatocytes, and round spermatids. These studies define conditions for monitoring protein synthesis in isolated spermatogenic cells prior to the pachytene stage of meiosis, provide a 2D map of proteins synthesized at these earlier meiotic stages, and examine the synthesis of several proteins previously identified on 2D gels with biochemical and immunological methods. 相似文献
11.
Protein sumoylation regulates a variety of nuclear functions and has been postulated to be involved in meiotic chromosome dynamics as well as other processes of spermatogenesis. Here, the expression and distribution of sumoylation pathway genes and proteins were determined in mouse male germ cells, with a particular emphasis on prophase I of meiosis. Immunofluorescence microscopy revealed that SUMO1, SUMO2/3 and UBE2I (also known as UBC9) were localized to the XY body in pachytene and diplotene spermatocytes, while only SUMO2/3 and UBE2I were detected near centromeres in metaphase I spermatocytes. Quantitative RT-PCR and Western blotting were used to examine the expression of sumoylation pathway genes and proteins in enriched preparations of leptotene/zygotene spermatocytes, prepubertal and adult pachytene spermatocytes, as well as round spermatids. Two general expression profiles emerged from these data. The first profile, where expression was more prominent during meiosis, identified sumoylation pathway participants that could be involved in meiotic chromosome dynamics. The second profile, elevated expression in post-meiotic spermatids, suggested proteins that could be involved in spermiogenesis-related sumoylation events. In addition to revealing differential expression of protein sumoylation mediators, which suggests differential functioning, these data demonstrate the dynamic nature of SUMO metabolism during spermatogenesis. 相似文献
12.
Synaptonemal polycomplexes in spermatocytes of the gooseneck barnacle,Pollicipes polymerus Sowerby (Crustacea: Cirripedia) 总被引:1,自引:1,他引:0
Patricia L. Dudley 《Chromosoma》1973,40(3):221-242
Polycomplexes are described for the first time in spermatocytes of a cirripede crustacean, Pollicipes polymerus Sowerby. Synaptonemal complexes of regular tripartite construction are seen from zygotene to mid-pachytene. Although some of the synaptonemal complexes are disrupted at late pachytene and may degenerate at this stage, some persist and by diplotene may form polycomplexes by the bending and self-fusion of their lateral elements. These polycomplexes are still encompassed by chromosomes and consist of four dense plates and intercalated central elements and transverse fibers. Other polycomplexes with five or six dense plates, all of which are considerably wider than lateral elements of mid-pachytene synaptonemal complexes, are also seen in diplotene nuclei. These may be attached to a chromosome at only one end or may be in the nucleoplasm, free of chromosomal involvement except for fine fibrous connectives. No polycomplexes are seen in meiotic cells after diplotene and their fate is unknown. It is suggested that poly-complexes serve as sequestra for synaptonemal material which could prevent normal chromosomal disjunction. 相似文献
13.
Ultrastructural changes in the nuclear and cytoplasmic elements in the germ cells of female rats were followed before meiotic prophase (15.50 days post-co?tum and 17.25 days post-co?tum) and during it (17.75 days post-co?tum to birth). We observed: modifications in the nuclear envelope which was thick during the oogonial stage, becoming thinner when the chromosomes entered preleptotene stage. The thinning of the envelope was due to the disappearance of the chromatin material lining it; variations in the number and distribution of germ cell nuclear pores according to stage; the pores were first scattered in small clusters of 6 to 8 over the entire nuclear membrane. From the preleptotene to zygotene stage, these clusters enriched in pores to form large areas. Finally, in the pachytene and diplotene stages, clusters of more than 100 pores were seen; nucleolar fragmentation from the preleptotene stage, followed by the formation of a new active nucleole in the diplotene; polarization of the mitochondria in the oldest oogonia just before the beginning of meiotic prophase. This polarization disappeared after the onset of the meiotic processes, then appeared again near the developing Golgi apparatus at the end of the pachytene stage; the formation of large gap junctions and numerous bands of tight junctions between the somatic cells; these formations contrasted with small gap junctions, and the tight junctions became scarce just before the meiotic process began. These observations, as well as those concerning nuclear pore distribution were made using the cryofracture technique. 相似文献
14.
The temporal and spatial distribution of the proliferation associated Ki-67 protein during female and male meiosis 总被引:2,自引:0,他引:2
We used immunolocalization in tissue sections and cytogenetic preparations of female and male gonads to study the distribution of the proliferation marker pKi-67 during meiotic cell cycles of the house mouse, Mus musculus. During male meiosis, pKi-67 was continuously present in nuclei of all stages from the spermatogonium through spermatocytes I and II up to the earliest spermatid stage (early round spermatids) when it appeared to fade out. It was not detected in later spermatid stages or sperm. During female meiosis, pKi-67 was present in prophase I oocytes of fetal ovaries. It was absent in oocytes from newborn mice and most oocytes of primordial follicles from adults. The Ki-67 protein reappeared in oocytes of growing follicles and was continuously present up to metaphase II. Thus, pKi-67 was present in all stages of cell growth and cell division while it was absent from resting oocytes and during the main stages of spermiocytogenesis. Progression through the meiotic cell cycle was associated with extensive intranuclear relocation of pKi-67. In the zygotene and pachytene stages, most of the pKi-67 colocalized with centromeric (centric and pericentric) heterochromatin and adjacent nucleoli; the heterochromatic XY body in male pachytene, however, was free of pKi-67. At early diplotene, pKi-67 was mainly associated with nucleoli. At late diplotene, diakinesis, metaphase I and metaphase II of meiosis, pKi-67 preferentially bound to the perichromosomal layer and was almost absent from the heterochromatic centromeric regions of the chromosomes. After the second division of male meiosis, the protein reappeared at the centromeric heterochromatin and an adjacent region in the earliest spermatid stage and then faded out. The general patterns of pKi-67 distribution were comparable to those in mitotic cell cycles. With respect to the timing, it is interesting to note that relocation from the nucleolus to the perichromosomal layer takes place at the G2/M-phase transition in the mitotic cell cycle but at late diplotene of prophase I in meiosis, suggesting physiological similarity of these stages. 相似文献
15.
Immunochemical localization of contractile proteins in mammalian meiotic chromosomes 总被引:4,自引:0,他引:4
Prof. C. De Martino E. Capanna M. R. Nicotra P. G. Natali 《Cell and tissue research》1980,213(1):159-178
Summary Smooth muscle heavy myosin and actin have been detected in mouse and rat meiotic chromosomes, by indirect immunofluorescence performed on testis cryostat sections and isolated germ cells. Both contractile proteins are detectable in the nuclei of meiotic cells during the first prophase. The appearance and disappearance time of myosin and actin, however, is not synchronous. While actin is visible in small spots from resting to late diplotene spermatocytes, myosin appears as filaments in the primary spermatocytes from the zygotene to the early stage of diplotene. The number of myosin filaments in the pachytene spermatocytes corresponds to the number of bivalent chromosomes, whereas actin spots constantly outnumber the pairing chromosomes by two units. These immunochemical observations suggest that the two contractile proteins are associated with the synaptonemal complex (SC). Myosin seems to be associated with the central region of the SC, while actin is present in its basal knob which is in connection with the nuclear membrane. The difference in number between myosin filaments and actin spots appears to be related to the peculiar behaviour of the pairing sex chromosomes. The presence of contractile proteins in the nuclei of primary spermatocytes seems to suggest that they might play a role in the process of pairing of homologous chromosomes. 相似文献
16.
To begin to examine the function of the A-type cyclins during meiosis in the male, we have examined the developmental and cellular distribution of the cyclin A1 and cyclin A2 proteins, as well as their candidate cyclin-dependent kinase partners, Cdk1 and Cdk2, in the spermatogenic lineage. Immunohistochemical localization revealed that cyclin A1 is present only in male germ cells just prior to or during the first, but not the second, meiotic division. By contrast, cyclin A2 was expressed in spermatogonia and was most abundant in preleptotene spermatocytes, cells which will enter the meiotic pathway. Immunohistochemical detection of Cdk1 was most apparent in early pachytene spermatocytes, while staining intensity diminished in diplotene and meiotically dividing spermatocytes, the cells in which cyclin A1 expression was strongest. Cdk2 was highly expressed in all spermatocytes. Notably, in cells undergoing the meiotic reduction divisions, Cdk2 appeared to localize specifically to the chromatin. This was not the case for spermatogonia undergoing mitotic divisions. In the testis, cyclin A1 has been shown to bind both Cdk1 and Cdk2 but we show here that cyclin A2 binds only Cdk2. These results indicate that the A-type cyclins and their associated kinases have different functions in the initiation and passage of male germ cells through meiosis. 相似文献
17.
Cyclin A1-deficient mice lack histone H3 serine 10 phosphorylation and exhibit altered aurora B dynamics in late prophase of male meiosis 总被引:3,自引:0,他引:3
Male mice lacking cyclin A1 protein are sterile. Their sterility results from an arrest in the meiotic cell cycle of spermatocytes, which we now identify as occurring at late diplotene, immediately before diakinesis. The stage of arrest in cyclin A1-deficient mice is distinct from the arrest seen in spermatocytes that are deficient in its putative catalytic partner Cdk2, which occurs much earlier in pachytene. The arrest in cyclin A1-deficient spermatocytes is also accompanied by an unusual clustering of centromeric heterochromatin. Consistent with a possible defect in the centromeric region, immunofluorescent staining of cyclin A1 protein shows localization in the region of the centromere. Phosphorylation of histone H3 at serine 10 in pericentromeric heterochromatin, which normally occurs in late diplotene, is reduced in spermatocytes from heterozygous Ccna1(+/-) testes and completely absent in spermatocytes with no cyclin A1 protein. Concomitantly, the levels of pericentromeric aurora B kinase, known to phosphorylate histone H3 during meiosis, are partially reduced in spermatocytes from testes of heterozygous mice and further reduced in homozygous null spermatocytes. These data suggest a critical and concentration-dependent function for cyclin A1 in the pericentromeric region in late diplotene of meiosis, perhaps in assembly or function of the passenger protein complex. 相似文献
18.
A novel testis-specific protein, termed LRTP, was identified by screening both human and mouse testis and mouse pachytene spermatocyte cDNA libraries. Sequence analyses (GenBank accession number: AF092208) revealed that LRTP contains an amino terminus leucine-rich repeat domain. There are several acidic regions rich in glutamic acid in the C-terminus. The sequence, by GenBank search, shows similarities to LANP and SDS22+, leucine-rich repeat proteins localized to the nucleus and involved in the regulation of protein phosphatases. In mouse, the mRNA is first detected at about Day 14 postpartum, presumably when mid-pachytene spermatocytes are first seen. In situ hybridization confirmed the expression of the LRTP mRNA at this stage of spermatogenesis. Immunohistochemical analysis revealed that the protein is most abundant in the cytoplasm of pachytene and diplotene cells, corresponding to late prophase of meiosis I. Immunohistochemical localization is markedly reduced in secondary spermatocytes, suggesting a functional association of LRTP with meiosis. An LRTP cDNA probe did not bind to mouse ovary RNA in a dot blot assay. 相似文献
19.
Meiotic telomere distribution and Sertoli cell nuclear architecture are altered in Atm- and Atm-p53-deficient mice
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Scherthan H Jerratsch M Dhar S Wang YA Goff SP Pandita TK 《Molecular and cellular biology》2000,20(20):7773-7783
The ataxia telangiectasia mutant (ATM) protein is an intrinsic part of the cell cycle machinery that surveys genomic integrity and responses to genotoxic insult. Individuals with ataxia telangiectasia as well as Atm(-/-) mice are predisposed to cancer and are infertile due to spermatogenesis disruption during first meiotic prophase. Atm(-/-) spermatocytes frequently display aberrant synapsis and clustered telomeres (bouquet topology). Here, we used telomere fluorescent in situ hybridization and immunofluorescence (IF) staining of SCP3 and testes-specific histone H1 (H1t) to spermatocytes of Atm- and Atm-p53-deficient mice and investigated whether gonadal atrophy in Atm-null mice is associated with stalling of telomere motility in meiotic prophase. SCP3-H1t IF revealed that most Atm(-/-) p53(-/-) spermatocytes degenerated during late zygotene, while a few progressed to pachytene and diplotene and some even beyond metaphase II, as indicated by the presence of a few round spermatids. In Atm(-/-) p53(-/-) meiosis, the frequency of spermatocytes I with bouquet topology was elevated 72-fold. Bouquet spermatocytes with clustered telomeres were generally void of H1t signals, while mid-late pachytene and diplotene Atm(-/-) p53(-/-) spermatocytes displayed expression of H1t and showed telomeres dispersed over the nuclear periphery. Thus, it appears that meiotic telomere movements occur independently of ATM signaling. Atm inactivation more likely leads to accumulation of spermatocytes I with bouquet topology by slowing progression through initial stages of first meiotic prophase and an ensuing arrest and demise of spermatocytes I. Sertoli cells (SECs), which contribute to faithful spermatogenesis, in the Atm mutants were found to frequently display numerous heterochromatin and telomere clusters-a nuclear topology which resembles that of immature SECs. However, Atm(-/-) SECs exhibited a mature vimentin and cytokeratin 8 intermediate filament expression signature. Upon IF with ATM antibodies, we observed ATM signals throughout the nuclei of human and mouse SECs, spermatocytes I, and haploid round spermatids. ATM but not H1t was absent from elongating spermatid nuclei. Thus, ATM appears to be removed from spermatid nuclei prior to the occurrence of DNA nicks which emanate as a consequence of nucleoprotamine formation. 相似文献