Detection of nondisjunction in mammals

Abstract

Methods have been developed in the past to assess spontaneous and induced chromosomal aneuploidy in germ cells and in early pre- and postimplantation mammalian embryos. Some of these methods yield still more information when combined with chromosome banding techniques. Various chemicals and x-rays have been tested in mammalian oogenesis and x-rays in spermatogenesis. The inference may be drawn from these studies that spontaneous nondisjunction is considered to occur only rarely in mouse and hamster oogenesis and spermatogenesis. X-rays induce nondisjunction during male and femlae meiosis, thus giving rise to significantly more aneuploid oocytes and F1 embryos. The alkylating agents trenimone and cyclophosphamide induce chromosomal missegregation in oocytes; the incidence depends on the dose injected. Hormones used as oral contraceptives did cause aneuploidy in oocytes, but only after daily treatment with high doses. Hormones used for stimulated ovulation did not interfere with chromosome segregation in the mouse and Chinese and Syrian hamsters. The following problems may be considered in futre studies: the problem of a species-specificity for induced nondisjunction; the question of a stage sensitivity (transplacental treatment); what happens after chronic exposure, also at low doses; the presence of a threshold; the existence of a dose-effect relation; the nature of cellular target(s) responsible for induced nondisjunction (spindle, regulatory proteins for polymerization of microtubules and ther depolymerization, centrioles, centromeres, RNA, or gene expression); whether DNA is involved and whether repair capacity plays a role.