The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Protamine 2 Deficiency Leads to Sperm DNA Damage and Embryo Death in Mice1
Abstract
Cytokinesis is incomplete in spermatogenic cells, and the descendants of each stem cell form a clonal syncytium. As a result, a heterozygous mutation in a gene expressed postmeiotically affects all of the haploid spermatids within a syncytium. Previously, we have found that disruption of one copy of the gene for either protamine 1 (PRM1) or protamine 2 (PRM2) in the mouse results in a reduction in the amount of the respective protein, abnormal processing of PRM2, and inability of male chimeras to transmit either the mutant or wild-type allele derived from the 129-genotype embryonic stem cells to the next generation. Although it is believed that protamines are essential for compaction of the sperm nucleus and to protect the DNA from damage, this has not been proven experimentally. To test the hypothesis that failure of chimeras to transmit the 129 genotype to offspring was due to alterations in the organization and integrity of sperm DNA, we used the single-cell DNA electrophoresis (comet) assay, ultrastructural analysis, and the intracytoplasmic sperm injection (ICSI) procedure. Comet assay demonstrated a direct correlation between the fraction of sperm with haploinsufficiency of PRM2 and the frequency of sperm with damaged DNA. Ultrastructural analysis revealed reduced compaction of the chromatin. ICSI with PRM2-deficient sperm resulted in activation of most metaphase II-arrested mouse eggs, but few were able to develop to the blastocyst stage. These findings suggest that development fails because of damage to paternal DNA and that PRM2 is crucial for maintaining the integrity of sperm chromatin.
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Cites
EVENSON, D. P., LARSON, K. L., & JOST, L. K. (2002) · Journal of Andrology · doi:10.1002/j.1939-4640.2002.tb02599.x · Cited by 1,072 · cited 1×
“The defects in condensation of sperm chromatin seen in mice with heterozygous mutations in Prm1 and Prm2 [2] also occurred when a transgene-expressing avian protamine was expressed in spermatids [26]; in null mutations of Tp1 [19], Tp2 [20], and Csnk2a2 [27]; with suppression of Prm1 translation in MSY4 gain-of-functi…”
Background
Cited by
The protamine family of sperm nuclear proteins
Balhorn, R. (2007) · Genome Biology · doi:10.1186/gb-2007-8-9-227 · Cited by 773
Sperm chromatin structure and male fertility: biological and clinical aspects
Erenpreiss, J., Spano, M., Erenpreisa, J., Bungum, M., & Giwercman, A. (2006) · Asian Journal of Andrology · doi:10.1111/j.1745-7262.2006.00112.x · Cited by 304
The sperm epigenome and potential implications for the developing embryo
Jenkins, T. G., & Carrell, D. T. (2012) · Reproduction · doi:10.1530/rep-11-0450 · Cited by 232
Bareh, G. M., Jacoby, E., Binkley, P., Chang, T.-C. “., Schenken, R. S., & Robinson, R. D. (2016) · Fertility and Sterility · doi:10.1016/j.fertnstert.2015.10.033 · Cited by 82
Hamad, M. F., Shelko, N., Kartarius, S., Montenarh, M., & Hammadeh, M. E. (2014) · Andrology · doi:10.1111/j.2047-2927.2014.00245.x · Cited by 81
Metadata
- Authors
- Cho, C., Jung-Ha, H., Willis, W. D., Goulding, E. H., Stein, P., Xu, Z., Schultz, R. M., Hecht, N. B., & Eddy, E. M.
- Venue
- Biology of Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-07-01
- Volume
- 69
- Issue
- 1
- Pages
- 211-217
- ISSN
- 0006-3363 (ISSN-L)
- 1529-7268
- OpenAlex
- W2137177802
- Cited by
- 367
- References
- 1
- FWCI
- 15.42
- Type
- journal article
- Language
- en
- Open access
- closed
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- Cho, C., Jung-Ha, H., Willis, W. D., Goulding, E. H., Stein, P., Xu, Z., Schultz, R. M., Hecht, N. B., & Eddy, E. M. (2003). Protamine 2 Deficiency Leads to Sperm DNA Damage and Embryo Death in Mice1. Biology of Reproduction. https://doi.org/10.1095/biolreprod.102.015115
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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