SPERM SELECTION, HETEROPLOIDY AND UNDERLYING MECHANISM

精子选择、异倍体和潜在机制

基本信息

批准号：
3316204
负责人：
PATRICIA ANASTASIA DELEON
金额：
$ 6.8万
依托单位：
UNIVERSITY OF DELAWARE
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-07-01 至 1988-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3316204
关键词：
aging animal population genetics chromosome translocation cyclic AMP diploidy embryo /fetus fertilization haploidy in vitro fertilization microscopy radioimmunoassay sperm sperm motility

项目摘要

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.

染色体不平衡的精子显着影响精子发生的频率活产和胎儿丢失中的异倍体。染色体研究仓鼠卵子体外受精后的人类精子表现出高个体差异显着的异倍体率频率。这些研究的解释要谨慎，因为种间杂交和受精条件。尽管如此，他们建议体内精子选择或合子后失去不平衡胚胎来解释高异倍体率。迄今为止，证据对于精子的选择一直是相互矛盾的。然而，最近的细胞遗传学对精子老化产生的单细胞受精卵的研究提供了强有力的证据精子选择过程可以在精子选择后放宽的证据男性的衰老。这些研究还表明，个人体外研究中发现的人类精子异倍体的变化可能这是由于受测男性精子老化的差异造成的。精子本文将研究选择和可能的潜在机制通过在小鼠中测试以下假设，使用一种新方法。 1）有一种针对非整倍体精子的选择机制易位携带者和精子老化后可以放松男性。 2）施肥频率的个体差异染色体正常男性的异倍体精子可能与年龄有关受精时的精子数量。 3）由于未老龄人群中精子成熟延迟、染色体不平衡在体内受精方面处于选择性劣势，但并非如此体外。 4）异倍体精子与正常精子的差异成熟和/或衰老水平可能与精子选择有关。第一个可以分析受精精子的裂解测定基因组（以及雌性）在种内杂交中，并消除了合子后丢失问题将用于染色体研究。年老且未老化的单倍体和二倍体精子将进行细胞化学测量核蛋白结构随成熟度的变化而存在差异。它们的 cAMP 含量随成熟度和将使用放射免疫测定来测量衰老。该研究与鉴于体外受精在人类中的应用不断增加，它非常重要而易位携带者应该对遗传感兴趣辅导员。