ACUTE EXPOSURE OF FEMALE HAMSTERS TO CARBENDAZIM (MBC) DURING MEIOSISRESULTS IN ANEUPLOID OOCYTES WITH SUBSEQUENT ARREST OF EMBRYONIC CLEAVAGE AND IMPLANTATION

A single oral dose of the fungicide and microtubule poison, MBC, admin istered to female hamsters at proestrus, results in infertility and ea rly pregnancy loss (1). To characterize the site and mode of action of this effect, direct assessments of oocyte chromosomes, fertilization, and preimplantation embryo development were made, Female hamsters wer e given a single dose of MBC (1000 mg/kg) on the afternoon of proestru s (to coincide with meiotic maturation of the oocytes) and either kill ed shortly after ovulation (day 1) to recover oocytes, or bred and kil led on gestation day (gd) 1 to 5 of pregnancy to assess fertilization and preimplantation embryo development and enumerate early implantatio n sites, Chromosome analysis in unfertilized oocytes revealed an MBC-i nduced increase in aneuploidy (37 vs, 14% in controls), When animals w ere bred after dosing, MBC had no effect on the number of oocytes reco vered or fertilized, However, significant increases were found in the proportion of embryos that failed to reach the expected stage of devel opment, namely, the eight-cell stage on the afternoon of gd 3, the mor ula stage by the morning of gd 4, and the blastocyst stage by the afte rnoon of gd 4 (a time when some embryos have implanted), The mean numb er of implantation sites, revealed by Evans Blue staining, was also si gnificantly lower in treated females on the afternoon of gd 4 and the morning of gd 5, These simple direct assessments elucidated a mechanis m of MBC-induced early pregnancy loss, induction of aneuploidy in oocy tes, They also ruled out an effect on fertilization, but demonstrated a subsequent arrest of preimplantation embryonic development accompani ed by a decrease in the likelihood of implantation.