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Cancer Epidemiology Aug 2018The incidence of testicular cancer in the United States (US) has substantially increased in recent decades. The majority of testicular cancers are germ cell tumors...
BACKGROUND
The incidence of testicular cancer in the United States (US) has substantially increased in recent decades. The majority of testicular cancers are germ cell tumors (TGCT), which are the most commonly occurring malignancies among men aged 15-44 years in the US. To date, few studies have focused on testicular cancer among men aged ≥ 50 years. Thus, we sought to examine detailed descriptive features, including incidence rates and age patterns, of tumors that arise in the testes among men aged ≥ 50 years.
METHODS
Data from forty-one US cancer registries were included for the years 1999-2014. Incidence rates per 100,000 person-years and their 95% confidence intervals (CI) were calculated by race/ethnicity, histology, and age at diagnosis. Estimates of annual percent change (APC) were also calculated.
RESULTS
Age-specific incidence rates of spermatocytic tumors, sex cord stromal tumors and lymphomas rose with age, while age-specific incidence rates of seminomas and nonseminomas declined. Between 1999 and 2014, the incidence of nonseminoma (APC = 3.26, 95% CI: 2.27-4.25) increased more than any other tumor type. The incidence of seminoma (APC: 1.15, 95% CI: 0.59-1.71) also increased, while rates of testicular lymphoma (APC: -0.66, 95% CI: -1.16 to -0.16), spermatocytic tumors (APC: 0.42, 95% CI: -1.42 to 2.29), and sex cord stromal tumors (APC: 0.60, 95% CI: -3.21 to 4.55) remained relatively unchanged.
CONCLUSION
Given the distinct time-trends and age-specific patterns of testicular cancer in men aged ≥50 years, additional investigation of risk factors for these tumors is warranted.
Topics: Aged; Aged, 80 and over; Ethnicity; Humans; Incidence; Male; Middle Aged; Neoplasms, Germ Cell and Embryonal; Racial Groups; Registries; Risk Factors; Seminoma; Spermatocytes; Testicular Neoplasms; United States
PubMed: 29807233
DOI: 10.1016/j.canep.2018.05.007 -
FEBS Open Bio Jan 2019Repression of retrotransposons is essential for genome integrity during germ cell development and is tightly controlled through epigenetic mechanisms. In primordial germ...
Repression of retrotransposons is essential for genome integrity during germ cell development and is tightly controlled through epigenetic mechanisms. In primordial germ cells, protein arginine -methyltransferase (Prmt5) is involved in retrotransposon repression by methylating Piwi proteins, which is part of the piRNA pathway. Here, we show that in mice, genetic inactivation of (which is highly expressed in testis and encodes a histone-binding protein required for the targeting of Prmt5 activity) affects the maturation of spermatogonia to spermatids. Mass spectrometry analysis revealed the presence of Miwi in testis protein lysates immunoprecipitated with an anti-Coprs antibody. The observed deregulation of Miwi and pachytene pre-piRNAs levels and the derepression of repetitive sequences observed in -/- mice suggest that Coprs is implicated in genome surveillance mechanisms.
Topics: Animals; Histone Chaperones; Long Interspersed Nucleotide Elements; Male; Mice; Mice, Knockout; Protein-Arginine N-Methyltransferases; Spermatocytes; Spermatogenesis
PubMed: 30652083
DOI: 10.1002/2211-5463.12562 -
Developmental Cell Aug 2012Basal bodies are freed from cilia and transition into centrioles to organize centrosomes in dividing cells. A mutually exclusive centriole/basal body existence during...
Basal bodies are freed from cilia and transition into centrioles to organize centrosomes in dividing cells. A mutually exclusive centriole/basal body existence during cell-cycle progression has become a widely accepted principle. Contrary to this view, we show here that cilia assemble and persist through two meiotic divisions in Drosophila spermatocytes. Remarkably, all four centrioles assemble primary cilia-centriole complexes that transit from the plasma membrane encased in a packet of membrane, recruit centrosomal material into microtubule-organizing centers, and persist at the spindle poles through division. Thus, spermatocyte centrioles organize centrosomes and cilia simultaneously at cell division. These findings challenge the prevailing view that cilia antagonize cell-cycle progression and raise the possibility that cilium retention at cell division may occur in diverse organisms and cell types.
Topics: Animals; Cell Division; Cilia; Drosophila melanogaster; Male; Microscopy, Electron, Transmission; Spermatocytes
PubMed: 22898783
DOI: 10.1016/j.devcel.2012.05.024 -
STAR Protocols Mar 2021Here, we describe a detailed protocol for the isolation of purified populations of viable spermatogenic cells derived from the non-human primate model organism ()....
Here, we describe a detailed protocol for the isolation of purified populations of viable spermatogenic cells derived from the non-human primate model organism (). Using fluorescence-activated cell sorting (FACS), we describe methods to isolate spermatogonia and primary spermatocytes ranging across the sub-stages of meiosis prophase I. These cell populations can be used with a variety of downstream assays, including single-cell approaches such as RNA sequencing, chromatin immunoprecipitation, quantitative RT-PCR, and immunocytochemistry. For complete details on the use and execution of this protocol, please refer to Lau et al (2020).
Topics: Animals; Cell Separation; Macaca fascicularis; Male; Spermatocytes; Testis
PubMed: 33532739
DOI: 10.1016/j.xpro.2021.100294 -
Molecular Biology of the Cell Mar 2019Cell differentiation is driven by changes in gene expression that manifest as changes in cellular phenotype or function. Altered cellular phenotypes, stemming from...
Cell differentiation is driven by changes in gene expression that manifest as changes in cellular phenotype or function. Altered cellular phenotypes, stemming from genetic mutations or other perturbations, are widely assumed to directly correspond to changes in the transcriptome and vice versa. Here, we exploited the cytologically well-defined Prdm9 mutant mouse as a model of developmental arrest to test whether parallel programs of cellular differentiation and gene expression are tightly coordinated, or can be disassociated. By comparing cytological phenotype markers and transcriptomes in wild-type and mutant spermatocytes, we identified multiple instances of cellular and molecular uncoupling in Prdm9 mutants. Most notably, although Prdm9 germ cells undergo cytological arrest in a late-leptotene/zygotene stage, they nevertheless develop gene expression signatures characteristic of later developmental substages. These findings suggest that transcriptomic changes may not reliably map to cellular phenotypes in developmentally perturbed systems.
Topics: Animals; Cell Differentiation; Gene Expression Regulation; Histone-Lysine N-Methyltransferase; Male; Meiosis; Mice, Inbred C57BL; Models, Biological; Mutation; Phenotype; RNA, Messenger; Spermatocytes; Testis; Transcriptome
PubMed: 30649999
DOI: 10.1091/mbc.E18-10-0681 -
Proceedings of the National Academy of... May 2019Faithful chromosome segregation during meiosis I depends upon the formation of connections between homologous chromosomes. Crossovers between homologs connect the...
Faithful chromosome segregation during meiosis I depends upon the formation of connections between homologous chromosomes. Crossovers between homologs connect the partners, allowing them to attach to the meiotic spindle as a unit, such that they migrate away from one another at anaphase I. Homologous partners also become connected by pairing of their centromeres in meiotic prophase. This centromere pairing can promote proper segregation at anaphase I of partners that have failed to become joined by a crossover. Centromere pairing is mediated by synaptonemal complex (SC) proteins that persist at the centromere when the SC disassembles. Here, using mouse spermatocyte and yeast model systems, we tested the role of shugoshin in promoting meiotic centromere pairing by protecting centromeric synaptonemal components from disassembly. The results show that shugoshin protects the centromeric SC in meiotic prophase and, in anaphase, promotes the proper segregation of partner chromosomes that are not linked by a crossover.
Topics: Anaphase; Animals; Cell Cycle Proteins; Centromere; Chromosome Segregation; Male; Mice; Mice, Knockout; Prophase; Saccharomyces cerevisiae; Spermatocytes; Spindle Apparatus; Synaptonemal Complex
PubMed: 31019073
DOI: 10.1073/pnas.1902526116 -
Birth Defects Research. Part B,... Feb 20152-Hydroxy-4-methoxybenzophenone (HMB) is an ultraviolet (UV) absorbing compound used in many cosmetic products as a UV-protecting agent and in plastics for preventing...
BACKGROUND
2-Hydroxy-4-methoxybenzophenone (HMB) is an ultraviolet (UV) absorbing compound used in many cosmetic products as a UV-protecting agent and in plastics for preventing UV-induced photodecomposition. HMB has been detected in over 95% of randomly collected human urine samples from adults and from premature infants, and it may have estrogenic potential.
METHODS
To determine the effects of maternal and lactational exposure to HMB on development and reproductive organs of offspring, time-mated female Harlan Sprague-Dawley rats were dosed with 0, 1000, 3000, 10,000, 25,000, or 50,000 ppm HMB (seven to eight per group) added to chow from gestation day 6 until weaning on postnatal day (PND) 23.
RESULTS AND CONCLUSION
Exposure to HMB was associated with reduced body and organ weights in female and male offspring. No significant differences were observed in the number of implantation sites/litter, mean resorptions/litter, % litters with resorptions, number and weights of live fetuses, or sex ratios between the control and HMB dose groups. Normalized anogenital distance in male pups at PND 23 was decreased in the highest dose group. Spermatocyte development was impaired in testes of male offspring in the highest dose group. In females, follicular development was delayed in the highest dose group. However, by evaluating levels of the compound in rat serum, the doses at which adverse events occurred are much higher than usual human exposure levels. Thus, exposure to less than 10,000 ppm HMB does not appear to be associated with adverse effects on the reproductive system in rats.
Topics: Animals; Animals, Newborn; Benzophenones; Body Weight; Cell Count; Embryonic Development; Female; Lactation; Male; Organ Size; Pregnancy; Prenatal Exposure Delayed Effects; Rats, Sprague-Dawley; Reproduction; Seminiferous Tubules; Spermatocytes; Testosterone
PubMed: 25707689
DOI: 10.1002/bdrb.21137 -
Biochimica Et Biophysica Acta.... Mar 2017Importin 13 (Imp13) is a bidirectional nuclear transporter of proteins involved in a range of important cellular processes, with an N-terminally truncated inhibitory...
Importin 13 (Imp13) is a bidirectional nuclear transporter of proteins involved in a range of important cellular processes, with an N-terminally truncated inhibitory isoform (tImp13) specifically expressed in testis. To gain insight into tImp13 function, we performed a yeast-2-hybrid screen from a human testis cDNA library, identifying for the first time a suite of interactors with roles in diverse cellular process. We validated the interaction of tImp13 with Eukaryotic translation initiation factor 4γ2 (EIF4G2) and High mobility group containing protein 20A (HMG20A), benchmarking that with glucocorticoid receptor (GR), a known Imp13 interactor expressed in testis. Coimmunoprecipitation assays indicated association of both tImp13 and Imp13 with EIF4G2, HMG20A and GR. Quantitative confocal microscopic analysis revealed the ability of tImp13 to inhibit the nuclear localisation of EIF4G2, HMG20A and GR, as well as that of Imp13 to act as a nuclear exporter for both EIF4G2 and HMG20A, and as a nuclear importer for GR. The physiological relevance of these results was highlighted by the cytoplasmic localisation of EIF4G2, HMG20A and GR in pachytene spermatocytes/round spermatids in the murine testis where tImp13 is present at high levels, in contrast to the nuclear localisation of HMG20A and GR in spermatogonia, where tImp13 is largely absent. Interestingly, Imp13, EIF4G2, HMG20A and GR were found together in the acrosome vesicle of murine epididymal spermatozoa. Collectively, our findings show, for the first time, that tImp13 may have a functional role in the mature spermatozoa, in addition to that in the meiotic germ cells of the testis.
Topics: Animals; Cell Nucleus; Eukaryotic Initiation Factor-4G; Gene Expression Regulation, Developmental; Gene Library; High Mobility Group Proteins; Humans; Karyopherins; Male; Mice; Protein Binding; Protein Interaction Mapping; Protein Isoforms; Protein Transport; Receptors, Glucocorticoid; Signal Transduction; Spermatids; Spermatocytes; Spermatogenesis; Testis; Two-Hybrid System Techniques
PubMed: 27993670
DOI: 10.1016/j.bbamcr.2016.12.017 -
European Journal of Histochemistry : EJH Jun 2016We investigated whether apoptotic spermatocytes from the mouse Mus m. domesticus presented alterations in chromosomal synapses and DNA repair. To enrich for apoptotic...
We investigated whether apoptotic spermatocytes from the mouse Mus m. domesticus presented alterations in chromosomal synapses and DNA repair. To enrich for apoptotic spermatocytes, the scrotum's temperature was raised by partially exposing animals for 15 min to a 42ºC water bath. Spermatocytes in initial apoptosis were identified in situ by detecting activated Caspase-9. SYCP1 and SYCP3 were markers for evaluating synapses or the structure of synaptonemal complexes and Rad51 and γH2AX for detecting DNA repair and chromatin remodeling. Apoptotic spermatocytes were concentrated in spermatogenic cycle stages III-IV (50.3%), XI-XII (44.1%) and IX-X (4.2%). Among apoptotic spermatocytes, 48% were in middle pachytene, 44% in metaphase and 6% in diplotene. Moreover, apoptotic spermatocytes showed several structural anomalies in autosomal bivalents, including splitting of chromosomal axes and partial asynapses between homologous chromosomes. gH2AX and Rad51 were atypically distributed during pachytene and as late as diplotene and associated with asynaptic chromatin, single chromosome axes or discontinuous chromosome axes. Among apoptotic spermatocytes at pachytene, 70% showed changes in the structure of synapses, 67% showed changes in gH2AX and Rad51 distribution and 50% shared alterations in both synapses and DNA repair. Our results showed that apoptotic spermatocytes from Mus m. domesticus contain a high frequency of alterations in chromosomal synapses and in the recruitment and distribution of DNA repair proteins. Together, these observations suggest that these alterations may have been detected by meiotic checkpoints triggering apoptosis.
Topics: Animals; Apoptosis; Caspase 9; Cell Cycle; Cell Cycle Proteins; Chromosome Pairing; DNA Repair; DNA-Binding Proteins; Male; Mice; Nuclear Proteins; Rad51 Recombinase; Spermatocytes
PubMed: 27349323
DOI: 10.4081/ejh.2016.2677 -
Epigenetics & Chromatin Apr 2018Meiosis is a specialized germ cell cycle that generates haploid gametes. In the initial stage of meiosis, meiotic prophase I (MPI), homologous chromosomes pair and...
BACKGROUND
Meiosis is a specialized germ cell cycle that generates haploid gametes. In the initial stage of meiosis, meiotic prophase I (MPI), homologous chromosomes pair and recombine. Extensive changes in chromatin in MPI raise an important question concerning the contribution of epigenetic mechanisms such as DNA methylation to meiosis. Interestingly, previous studies concluded that in male mice, genome-wide DNA methylation patters are set in place prior to meiosis and remain constant subsequently. However, no prior studies examined DNA methylation during MPI in a systematic manner necessitating its further investigation.
RESULTS
In this study, we used genome-wide bisulfite sequencing to determine DNA methylation of adult mouse spermatocytes at all MPI substages, spermatogonia and haploid sperm. This analysis uncovered transient reduction of DNA methylation (TRDM) of spermatocyte genomes. The genome-wide scope of TRDM, its onset in the meiotic S phase and presence of hemimethylated DNA in MPI are all consistent with a DNA replication-dependent DNA demethylation. Following DNA replication, spermatocytes regain DNA methylation gradually but unevenly, suggesting that key MPI events occur in the context of hemimethylated genome. TRDM also uncovers the prior deficit of DNA methylation of LINE-1 retrotransposons in spermatogonia resulting in their full demethylation during TRDM and likely contributing to the observed mRNA and protein expression of some LINE-1 elements in early MPI.
CONCLUSIONS
Our results suggest that contrary to the prevailing view, chromosomes exhibit dynamic changes in DNA methylation in MPI. We propose that TRDM facilitates meiotic prophase processes and gamete quality control.
Topics: Animals; DNA Methylation; Epigenesis, Genetic; Long Interspersed Nucleotide Elements; Male; Meiotic Prophase I; Mice; Molecular Sequence Annotation; Spermatocytes; Spermatogenesis; Spermatogonia; Spermatozoa; Testis; Whole Genome Sequencing
PubMed: 29618374
DOI: 10.1186/s13072-018-0186-0