SPERM SELECTION, HETEROPLOIDY AND UNDERLYING MECHANISM

精子选择、异倍体和潜在机制

• 批准号: 3316200
• 负责人: PATRICIA ANASTASIA DELEON
• 金额: $ 6.54万
• 依托单位: UNIVERSITY OF DELAWARE
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3316200
• 关键词: aging; animal population genetics; chromosome translocation; cyclic AMP; diploidy; embryo /fetus; fertilization; haploidy; in vitro fertilization; microscopy; radioimmunoassay; sperm; sperm motility

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对频率显着贡献 活出生和胎儿损失的杂质。 染色体的研究 仓鼠卵的体外受精后的人类精子表现出很高 异质体的速率具有明显的个体差异 频率。 这些研究被谨慎解释，因为 种间交叉和受精的条件。 尽管如此，他们还是 建议体内精子选择或同进行后不平衡的丧失 胚胎以考虑高杂质率。 迄今为止，证据 对于精子的选择一直存在冲突。 但是，最近的细胞遗传学 对精子衰老产生的单细胞合子的研究提供了强大的研究 精子后可以放松的精子选择过程的证据 男性衰老。 这些研究还表明个人 在体外研究中发现的人类精子异质的变化可能 是由于测试的雄性的精子衰老的变化而产生的。 精子 在本文中将研究选择和可能的潜在机制 通过测试鼠标中的以下假设，使用新方法。 1） 有一种选择机制针对非整倍型精子的精子 易位载体，可以在精子衰老后放松 男性。 2）施肥频率的个体差异 染色体正常男性的杂质精子可能与年龄有关 受精时的精子种群。 3）由于 成熟延迟，未衰老人群中的染色体不平衡精子 在体内影响施肥方面处于选择性劣势，但不存在 体外。 4）杂质和正常精子之间的差异 精子选择可能涉及成熟和/或衰老水平。 第一个裂解测定法，允许分析受精精子 基因组（以及女性）在种内交叉中，并消除了 染色体研究将使用后整体丧失的问题。 老化和 未染色的单倍体和二倍体精子将通过细胞化学测量 核蛋白结构的差异随成熟度的函数。 其营地内容的差异是成熟和 衰老将使用放射免疫测定法测量。 该研究与 鉴于其在人类中的使用越来越重要，体外受精很重要 而易位载体应该对遗传感兴趣 辅导员。