Aneuploidies and micronuclei in the germ cells of male mice of advanced age

Lowe, Xiu; Collins, Brad; Allen, James W.; Titenko-Holland, Nina; Breneman, John W.; Beek, M. van; Bishop, Jack B.; Wyrobek, Andrew J.

doi:10.1016/0921-8734(95)00012-u

Cited by 66 publications

(38 citation statements)

References 36 publications

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“…A relation between age and frequency of sperm disomy has been reported in both humans (Griffin et al, 1995;Martin et al, 1995;Robbins et al, 1995;Kinakin et al, 1997) and mice (Lowe et al, 1995). No age dependence of the frequencies of sperm disomy or diploidy was demonstrable in the boars tested in our laboratory.…”

Section: Discussionmentioning

confidence: 71%

Aneuploidy in pig sperm: multicolor fluorescence in situ hybridization using probes for chromosomes 1, 10, and Y

Rubeš

Vozdová

Kubı́čková

1999

Cytogenet Genome Res

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The objective of this research was to develop chromosome-specific probes for use in evaluating aneuploidy in boar spermatozoa through the application of fluorescence in situ hybridization (FISH) technology. A multicolor FISH method was developed to detect aneuploidy in the sperm of boars using DNA probes specific for small regions of chromosomes 1, 10, and Y. The average frequencies of sperm with disomy for chromosomes 1, 10, and Y were 0.075%, 0.067%, and 0.094%, respectively. The incidence of disomy did not differ significantly by chromosome. The average frequencies of diploidy were 0.177% for 1-1-10-10 and 0.022% for Y-Y-10-10. Thus, the incidence of overall diploidy (1-1-10-10) was significantly higher than that of disomy for the chromosomes examined (P < 0.01 for disomy of the autosomes and P < 0.05 for disomy of the Y chromosome). No significant age or breed effects on disomy and diploidy rates and no significant interindividual variations in disomy or diploidy were found. The observed level of numerical chromosome aberrations in pig sperm appear to be within the range of the baseline frequencies reported so far in men.

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Section: Discussionmentioning

confidence: 71%

Aneuploidy in pig sperm: multicolor fluorescence in situ hybridization using probes for chromosomes 1, 10, and Y

Rubeš

Vozdová

Kubı́čková

1999

Cytogenet Genome Res

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“…Several autosomal dominant genetic diseases due to de novo male germ line mutations are associated with increased paternal age (18,21,45,49), suggesting that male germ line genomic stability is compromised with age. Analysis of chromosomes in spermatozoa revealed an increased frequency of aberrations with age (24,34,41,54), providing additional evidence that male germ line genomic stability decreases with age. Similarly in mice, the spontaneous mutant frequency in a lacI transgene recovered from pachytene spermatocytes, round spermatids, and epididymal spermatozoa obtained from old animals was approximately 10-fold higher than the mutant frequency observed for young mice (60).…”

mentioning

confidence: 95%

Base Excision Repair Is Limited by Different Proteins in Male Germ Cell Nuclear Extracts Prepared from Young and Old Mice

Intano

McMahan

McCarrey

et al. 2002

Molecular and Cellular Biology

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The combined observations of elevated DNA repair gene expression, high uracil-DNA glycosylase-initiated base excision repair, and a low spontaneous mutant frequency for a lacI transgene in spermatogenic cells from young mice suggest that base excision repair activity is high in spermatogenic cell types. Notably, the spontaneous mutant frequency of the lacI transgene is greater in spermatogenic cells obtained from old mice, suggesting that germ line DNA repair activity may decline with age. A paternal age effect in spermatogenic cells is recognized for the human population as well. To determine if male germ cell base excision repair activity changes with age, uracil-DNA glycosylase-initiated base excision repair activity was measured in mixed germ cell (i.e., all spermatogenic cell types in adult testis) nuclear extracts prepared from young, middle-aged, and old mice. Base excision repair activity was also assessed in nuclear extracts from premeiotic, meiotic, and postmeiotic spermatogenic cell types obtained from young mice. Mixed germ cell nuclear extracts exhibited an age-related decrease in base excision repair activity that was restored by addition of apurinic/apyrimidinic (AP) endonuclease. Uracil-DNA glycosylase and DNA ligase were determined to be limiting in mixed germ cell nuclear extracts prepared from young animals. Base excision repair activity was only modestly elevated in pachytene spermatocytes and round spermatids relative to other spermatogenic cells. Thus, germ line shortpatch base excision repair activity appears to be relatively constant throughout spermatogenesis in young animals, limited by uracil-DNA glycosylase and DNA ligase in young animals, and limited by AP endonuclease in old animals.Germ line genomic stability is an important factor in reproductive health, with approximately 20% of genetic diseases attributed to new germ line mutations (12,13,46). Several autosomal dominant genetic diseases due to de novo male germ line mutations are associated with increased paternal age (18,21,45,49), suggesting that male germ line genomic stability is compromised with age. Analysis of chromosomes in spermatozoa revealed an increased frequency of aberrations with age (24, 34, 41, 54), providing additional evidence that male germ line genomic stability decreases with age. Similarly in mice, the spontaneous mutant frequency in a lacI transgene recovered from pachytene spermatocytes, round spermatids, and epididymal spermatozoa obtained from old animals was approximately 10-fold higher than the mutant frequency observed for young mice (60).In contrast to the decline in germ line genetic integrity with old age, the germ line DNA of young mice appears to be well maintained. Compared to somatic tissues, a lower spontaneous mutant frequency in the male germ line for a lacI transgene has been reported for fish (65), mice (32, 60), and rats (16). The murine mitotically proliferating male germ cell pool is comprised of primitive type A spermatogonia, which sequentially give rise to mitotically active, type ...

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“…About 3 sperm per 10,000 cells evaluated showed XX or 88 aneuploidies (Figure 7). 7 The frequencies we found for these particular numerical errors in two strains of mice were indistinguishable from those for sperm from healthy men using similar procedures and scoring methods. This work serves to demonstrate what we call "bridging biomarkers" between humans and animals for detecting sperm aneuploidy.…”

Section: How Fish Is Used To Detect Aneuploid Spermmentioning

confidence: 77%

Technologies for improving health care volume II

Fitch¹

1997

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financial and schedule penalties that result when perceived solutions drive a development process prior to understanding key issues. Our focused experimentation leverages sophisticated facilities and well-developed sensor and measurement capabilities to rapidly reach milestones. The Center also employs the world-class engineering capabilities at LLNL for developing prototypes rapidly. The Center's development programs often use computers to model and virtual-test concepts and designs as a cost-effective alternative to building prototypes and as an adjunct to experimental studies. The computer modeling often allows a broader design space to be explored without prototyping. In short, our approach to project management enables discovery, reduces overall costs, and accelerates development schedules.Funding for the Center is a combination of private sector, government, and the Lab's discretionary sources. Our customer-partners include government (federal and state), health-care organizations, and corporations. Our corporate customer-partners are usually market-and technology-driven companies that desire fresh technology perspectives, quick access to advanced technology and competencies that compliment their internal skills, and access to multidisciplinary programs and R&D without having to develop them. Our project teams address significant, unmet clinical and market needs that have the potential to reduce the human and economic costs of health care.

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Aneuploidies and micronuclei in the germ cells of male mice of advanced age

Cited by 66 publications

References 36 publications

Aneuploidy in pig sperm: multicolor fluorescence in situ hybridization using probes for chromosomes 1, 10, and Y

Aneuploidy in pig sperm: multicolor fluorescence in situ hybridization using probes for chromosomes 1, 10, and Y

Base Excision Repair Is Limited by Different Proteins in Male Germ Cell Nuclear Extracts Prepared from Young and Old Mice

Technologies for improving health care volume II

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