Chromosomally unbalanced sperm contribute significantly to the frequency of heteroploidy in live-births and fetal loss. Studies of chromosomes in human sperm after in vitro fertilization of hamster eggs have shown high rates of heteroploidy with significant individual differences in the frequency. These studies have been interpreted with caution because of the interspecies cross and the conditions of fertilization. Nevertheless, they suggest either in vivo sperm selection or postzygotic loss of unbalanced embryos to account for the high heteroploid rates. To date, the evidence for sperm selection has been conflicting. However, recent cytogenetic studies of one-cell zygotes resulting from sperm aging provide strong evidence for a sperm selection process that can be relaxed after sperm aging in the male. These studies also suggest that the individual variation in human sperm heteroploidy seen in the in vitro studies might have resulted from variation in sperm aging in the males tested. Sperm selection and possible underlying mechanisms will be investigated herein using a new approach by testing the following hypotheses in the mouse. 1) There is a selection mechanism operating against aneuploid sperm from translocation carriers and it can be relaxed after aging sperm in the male. 2) Individual differences in the frequency of fertilizing heteroploid sperm from chromosomally normal males may be related to the age of the sperm population at the time of fertilization. 3) Due to a maturational delay, chromosomally unbalanced sperm in unaged populations are at a selective disadvantage in effecting fertilization in vivo but not in vitro. 4) Differences between heteroploid and normal sperm in maturation and/or senescence levels may be involved in sperm selection. The first cleavage assay which allows analysis of the fertilizing sperm genome (as well as the female) in an intraspecies cross, and eliminates the question of postzygotic loss will be used for chromosome studies. Aged and unaged haploid and diploid sperm will be measured cytochemically for differences in the nucleoprotein structure as a function of maturity. Differences in their cAMP content as a function of maturation and senescence will be measured using a radioimmunoassay. The study with in vitro fertilization is important in light of its increasing use in man while that with translocation carriers should be of interest to genetic counselors.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
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Reproductive Biology Study Section (REB)
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University of Delaware
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Martin-DeLeon, P A (1989) Analysis of the chromosome complement in outbred mouse sperm fertilizing in vitro. Gamete Res 22:71-81
Martin-DeLeon, P A; McLaughlin, J; Mitzel, E et al. (1989) Mapping of the creatine kinase M gene to 19q11----q12 in the rabbit genome. Cytogenet Cell Genet 50:165-7
Zackowski, J L; Martin-DeLeon, P A (1989) Segregation products of male mice doubly heterozygous for the RB(6.16) and RB (16.17) translocations: influence of sperm karyotype on fertilizing competence under varying mating frequencies. Gamete Res 22:93-107
Tailor, S; Martin-DeLeon, P A (1989) Localization of the raf-1 protooncogene on chromosome 6 of the mouse. Cancer Genet Cytogenet 40:89-94
Shivashankar, L; Whitney, E; Colmorgen, G et al. (1988) Prenatal diagnosis of tetrasomy 47,XY,+i(12p) confirmed by in situ hybridization. Prenat Diagn 8:85-91
Zackowski, J L; Martin-Deleon, P A (1988) Second meiotic nondisjunction is not increased in postovulatory aged murine oocytes fertilized in vitro. In Vitro Cell Dev Biol 24:133-7
Martin-DeLeon, P A; Picciano, S R (1988) Localization of the KRAS2 oncogene in the domestic rabbit (Oryctolagus cuniculus). Cytogenet Cell Genet 48:201-4
Mahoney, C E; Picciano, S R; Burton, K M et al. (1988) Regional mapping of the creatine kinase b (CKBB) gene in rabbit (Oryctolagus cuniculus) and man using a rat cDNA probe. Cytogenet Cell Genet 48:160-3
Martin-DeLeon, P A; Picciano, S R (1988) In situ localization of murine c-Ki-ras-2 oncogene: preliminary evidence for conservation of telomeric territory of oncogenes? Somat Cell Mol Genet 14:205-10
Martin-DeLeon, P A; Muneses, C; Picciano, S et al. (1988) Differential silver staining in lymphocytes and lymphoblastoid cell cultures. Cytobios 55:113-23

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