FIRST-MEIOTIC-DIVISION NONDISJUNCTION IN HUMAN OOCYTES

Reject oocytes from in vitro-fertilization patients are currently the only practical source of human oocyte material available for meiotic s tudies in women. Two hundred clearly analyzable second meiotic (MII) m etaphase oocytes from 116 patients were examined for evidence of first meiotic (MI) division errors. The chromosome results, in which 67% of oocytes had a normal 23,X chromosome complement but none had an extra whole chromosome, cast doubt on the relevance, to human oocytes, of t hose theories of nondisjunction that propose that both chromosomes of the bivalent fail to disjoin at MI so that both move to one pole and r esult in an additional whole chromosome at MII metaphase. The only cla ss of abnormality found in the MII oocytes had single chromatids (half -chromosomes) replacing whole chromosomes. Analysis of the chromosomal ly abnormal oocytes revealed an extremely close correlation with data on trisomies in spontaneous abortions, with respect to chromosome dist ribution, frequency, and maternal age, and indicated the likelihood of the chromatid abnormalities being the MI-division nondisjunction prod ucts that lead to trisomy formation after fertilization. The most like ly derivation of the abnormalities is through a form of misdivision pr ocess usually associated with univalents, in which the centromeres div ide precociously at MI, instead of MII, division. In the light of rece nt data that show that altered recombination patterns of the affected chromosomes are a key feature of most MI-division trisomies, the oocyt e data imply that the vulnerable meiotic configurations arising from a ltered recombination patterns are processed as functional univalents i n older women. Preliminary evidence from MI-metaphase oocytes supports this view.