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ANEUPLOIDIES AND MICRONUCLEI IN THE GERM CELLS OF MALE MICE OF ADVANCED AGE
Citation:
Lowe, X., B. Allen, N. Titenko-Holland, J. Breneman, M. Beek, J. Bishop, AND A. Wyrobek. ANEUPLOIDIES AND MICRONUCLEI IN THE GERM CELLS OF MALE MICE OF ADVANCED AGE. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-95/550.
Description:
The objective of this research was to determine whether the frequencies of chromosomally defective germ cells increased with age in male laboratory mice. wo types of chromosomal abnormalities were characterized: (1) testicular spermatid aneuploidy (TSA) as measured by a new method of multi-color fluorescence in situ hybridization (FISH) with DNA probes specific for mouse chromosomes X, Y and 8, and (2) spermatid micronucleus (SMN) analyses using anti-kinetochore antibodies. 6C3Fl mice (aged 22.5 to 30.5 months, heavier than controls but otherwise in good health) showed significant - 2.0 fold increases in the aneuploidy phenotypes X-X-8, Y-Y-8, 8-8-X and 8-8-Y with the greatest effects appearing in animals aged greater than 28 months. o age effect was observed, however, in X-Y-8 hyperhaploidy. ajor age-related increases were seen in Y-Y-8 and X-X-8 hyperhaploidies suggesting that advanced paternal age is associated primarily with meiosis II rather than meiosis I disjunction errors. A 5-fold increase was also found in the frequency of micronucleated spermatids in aged mice when compared with ir young controls. ll micronuclei detected in the aged animals lacked kinetochore labeling, suggesting that they either did not contain intact chromosomes or the chromosomes lacked detectable kinetochores. he findings of the TSA and SMN assays are consistent with meiotic or premeiotic effects of advanced age on germ cell chromosomes, but USA there were differences in the age dependencies of aneuploidy and micronuclei. n summary, advanced paternal age may be a risk factor for chromosomal abnormalities (both aneuploidy and structural abnormalities) in male germ cells.