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 studies in women. Two hundred clearly analyzable second meiotic (MII) metaphase 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 those theories of nondisjunction that propose that both chromosomes of the bivalent fail to disjoin at MI so that both move to one pole and result in an additional whole chromosome at MII metaphase. The only class of abnormality found in the MII oocytes had single chromatids (half-chromosomes) replacing whole chromosomes. Analysis of the chromosomally abnormal oocytes revealed an extremely close correlation with data on trisomies in spontaneous abortions, with respect to chromosome distribution, frequency, and maternal age, and indicated the likelihood of the chromatid abnormalities being the MI-division nondisjunction products that lead to trisomy formation after fertilization. The most likely derivation of the abnormalities is through a form of misdivision process usually associated with univalents, in which the centromeres divide precociously at MI, instead of MII, division. In the light of recent data that show that altered recombination patterns of the affected chromosomes are a key feature of most MI-division trisomies, the oocyte data imply that the vulnerable meiotic configurations arising from altered recombination patterns are processed as functional univalents in older women. Preliminary evidence from MI-metaphase oocytes supports this view.