Complex chromosome rearrangements (CCRs) are structurally balanced or unbalanced aberrations involving more than two breakpoints on two or more chromosomes. CCRs can be a potential reason for genomic imbalance in gametes, which leads to a drastic reduction in fertility. In this study, the meiotic segregation pattern, aneuploidy of seven chromosomes uninvolved in the CCR and chromatin integrity were analysed in the ejaculated spermatozoa of a 46,XY,t(6;10;11)(q25.1;q24.3;q23.1)mat carrier with asthenozoospermia and a lack of conception. The frequency of genetically unbalanced spermatozoa was 78.8% with a prevalence of 4:2 segregants of 38.2%, while the prevalence of the adjacent 3:3 mode was 35.3%. Analysis of the aneuploidy of chromosomes 13, 15, 18, 21, 22, X and Y revealed an approximately fivefold increased level in comparison with that of the control group, indicating the presence of an interchromosomal effect. Sperm chromatin integrity status was evaluated using chromomycin A3 and aniline blue staining (deprotamination), acridine orange test and TUNEL assay (sperm DNA fragmentation). No differences were found when comparisons were made with a control group. We suggest that the accumulation of genetically unbalanced spermatozoa, significantly increased sperm aneuploidy level and decreased sperm motility (20%, progressive) were not responsible for the observed lack of reproductive success in the analysed infertile t(6;10;11) carrier. Interestingly, in the case described herein, a high level of sperm chromosomal imbalance appears not to be linked to sperm chromatin integrity status.
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http://dx.doi.org/10.1530/REP-13-0533 | DOI Listing |
Sci Rep
December 2024
Department of Pathology, Binzhou Medical University, Yantai, 264003, Shandong, China.
Accurate and timely genetic material replication is essential for preserving genomic integrity. The replication process begins with chromatin licensing and DNA replication factor 1 (CDT1). It has been demonstrated that dysregulated CDT1 expression causes genomic instability, damages DNA, and may even cause cancer.
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December 2024
Laboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:
A significant portion of human cancers utilize a recombination-based pathway, alternative lengthening of telomeres (ALT), to extend telomeres. To gain further insights into this pathway, we developed a high-throughput imaging-based screen named TAILS (telomeric ALT in situ localization screen) to identify genes that either promote or inhibit ALT activity. Screening over 1,000 genes implicated in DNA transactions, TAILS reveals both well-established and putative ALT modulators.
View Article and Find Full Text PDFVet Sci
December 2024
Clinic of Reproductive Medicine, Department for Farm Animals, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, CH-8057 Zurich, Switzerland.
Sperm viability is routinely assessed for the quality control of cryopreserved bovine sperm batches but is not usually conclusive regarding their fertilizing potential. In this study, we investigated the fertility predictive value of bull sperm viability in combination with DNA integrity or the functional status of viable sperm. In addition to sperm viability, we flow cytometrically assessed the percentage of sperm with high DNA fragmentation index (%DFI) and the fraction of viable sperm with low intracellular Ca content and functional mitochondria using the Sperm Chromatin Structure Assay and a five-color staining panel in 791 and 733 cryopreserved batches with non-return rate (NRR) records after ≥100 first services, respectively.
View Article and Find Full Text PDFReprod Biomed Online
September 2024
University of Technology Sydney, Sydney, Australia; Institute for Biomedical Materials and Devices, University of Technology Sydney, Sydney, Australia. Electronic address:
Research Question: Can a biomimetic microfluidic sperm sorter isolate motile sperm while minimizing DNA damage in comparison with density gradient centrifugation (DGC)?
Design: This was a two-phase study of 61 men, consisting of a proof-of-concept study with 21 donated semen samples in a university research laboratory, followed by a diagnostic andrology study with 40 consenting patients who presented at a fertility clinic for semen diagnostics. Each sample was split to perform DGC and microfluidic sperm selection (one-step sperm selection with 15 min of incubation) side-by-side. Outcomes evaluated included concentration, progressive motility, and DNA fragmentation index (DFI) of raw semen, and sperm isolated using DGC and the microfluidic device.
Cell Genom
December 2024
Department of Molecular & Medical Genetics, Oregon Health & Science University, Portland, OR, USA; Cancer Early Detection Advanced Research Institute, Oregon Health & Science University, Portland, OR, USA; Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA. Electronic address:
Single-cell methods to assess DNA methylation have not achieved the same level of cell throughput per experiment compared to other modalities, with large-scale datasets requiring extensive automation, time, and other resources. Here, we describe sciMETv3, a combinatorial indexing-based technique that enables atlas-scale libraries to be produced in a single experiment. To reduce the sequencing burden, we demonstrate the compatibility of sciMETv3 with capture techniques to enrich regulatory regions, as well as the ability to leverage enzymatic conversion, which can yield higher library diversity.
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