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DNA methylation modulates nucleosome retention in sperm and H3K4 methylation deposition in early mouse embryos.
Nat Commun
January 2025
Friedrich Miescher Institute for Biomedical Research, Fabrikstrasse 24, 4056, Basel, Switzerland.
In the germ line and during early embryogenesis, DNA methylation (DNAme) undergoes global erasure and re-establishment to support germ cell and embryonic development. While DNAme acquisition during male germ cell development is essential for setting genomic DNA methylation imprints, other intergenerational roles for paternal DNAme in defining embryonic chromatin are unknown. Through conditional gene deletion of the de novo DNA methyltransferases Dnmt3a and/or Dnmt3b, we observe that DNMT3A primarily safeguards against DNA hypomethylation in undifferentiated spermatogonia, while DNMT3B catalyzes de novo DNAme during spermatogonial differentiation.
View Article and Find Full Text PDFExploring the Epigenetic Landscape of Spermatozoa: Impact of Oxidative Stress and Antioxidant Supplementation on DNA Methylation and Hydroxymethylation.
Antioxidants (Basel)
December 2024
GReD Institute, Université Clermont Auvergne, Faculté de Médecine, CRBC, 28 Place Henri Dunant, 63001 Clermont-Ferrand, France.
Reproductive success is dependent on gamete integrity, and oxidative stress alters male nuclei, meaning that no DNA repair is possible due to chromatin compaction. The composition of sperm makes it highly sensitive to reactive oxygen species (ROS) but, at the same time, ROS are needed for sperm physiology. Over the past 30 years, much attention has been paid to the consequences of oxidative stress on sperm properties and the protective effects of antioxidant formulations to help fertility.
View Article and Find Full Text PDFSperm Functional Status: A Multiparametric Assessment of the Fertilizing Potential of Bovine Sperm.
Vet 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 PDFA biomimetic sperm selection device for routine sperm selection.
Reprod 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.
Environmentally-relevant doses of bisphenol A and S exposure in utero disrupt germ cell programming across generations resolved by single nucleus multi-omics.
bioRxiv
December 2024
School of Molecular Biosciences, Center for Reproductive Biology, Washington State University, 1770 NE Stadium Way, Pullman, WA, 99164, USA.
Background: Exposure to endocrine-disrupting chemicals (EDCs), such as bisphenol A (BPA), disrupts reproduction across generations. Germ cell epigenetic alterations are proposed to bridge transgenerational reproductive defects resulting from EDCs. Previously, we have shown that prenatal exposure to environmentally relevant doses of BPA or its substitute, BPS, caused transgenerationally maintained reproductive impairments associated with neonatal spermatogonial epigenetic changes in male mice.
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