Trichlorfon exposure, spindle aberrations and nondisjunction in mammalian oocytes

Consumption of trichlorfon-poisoned fish by women in a small Hungarian vill age has been associated with trisomy resulting from an error of meiosis B i n oogenesis. We therefore examined mouse oocytes exposed for 3 h during fer tilization to 50 mu g/ml trichlorfon. Spindle morphology was not visibly al tered by the pesticide. Chromosomes segregated normally at anaphase II with no induction of aneuploidy. However, formation of a spindle was disturbed in many oocytes resuming meiosis I in the presence of trichlorfon. In spite of the spindle aberrations and the failure of bivalents to align properly at the equator, oocytes did not become meiotically arrested but progressed to metaphase B. At this stage, spindles were highly abnormal, and chromosom es were often totally unaligned, unattached or dispersed on the elongated a nd disorganized spindle. By causing spindle aberrations and influencing chr omosome congression, trichlorfon appears, therefore, to predispose mammalia n oocytes to random chromosome segregation, especially when they undergo a first division and develop to metaphase II during exposure. This is the fir st case in which environmentally induced human trisomy can be correlated wi th spindle aberrations induced by chemical exposure. Our observations sugge st that oocytes may not possess a checkpoint sensing displacement of chromo somes from the equator at meiosis I and may therefore be prone to nondisjun ction.