Acute exposure of female hamsters to carbendazim (MBC) during meiosis results in aneuploid oocytes with subsequent arrest of embryonic cleavage and implantation.
A single oral dose of the fungicide and microtubule poison, MBC, administered to female hamsters at proestrus, results in infertility and early 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 were given a single dose of MBC (1,000 mg/kg) on the afternoon of proestrus (to coincide with meiotic maturation of the oocytes) and either killed shortly after ovulation (day 1) to recover oocytes, or bred and killed on gestation day (gd) 1 to 5 of pregnancy to assess fertilization and preimplantation embryo development and enumerate early implantation sites. Chromosome analysis in unfertilized oocytes revealed an MBC-induced increase in aneuploidy (37 vs. 14% in controls). When animals were bred after dosing, MBC had no effect on the number of oocytes recovered or fertilized. However, significant increases were found in the proportion of embryos that failed to reach the expected stage of development, namely, the eight-cell stage on the afternoon of gd 3, the morula stage by the morning of gd 4, and the blastocyst stage by the afternoon of gd 4 (a time when some embryos have implanted). The mean number of implantation sites, revealed by Evans Blue staining, was also significantly lower in treated females on the afternoon of gd 4 and the morning of gd 5. These simple direct assessments elucidated a mechanism of MBC-induced early pregnancy loss, induction of aneuploidy in oocytes. They also ruled out an effect on fertilization, but demonstrated a subsequent arrest of preimplantation embryonic development accompained by a decrease in the likelihood of implantation.
Jeffay
S C
SC
Reproductive Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Libbus
B L
BL
Barbee
R R
RR
Perreault
S D
SD
D000284:Administration, Oral; D000782:Aneuploidy; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000633:toxicity*; D002219:Carbamates; D002970:Cleavage Stage, Ovum / Q000187:drug effects*; D006224:Cricetinae; D010064:Embryo Implantation / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects; D005659:Fungicides, Industrial / Q000008:administration & dosage / Q000633:toxicity*; D008540:Meiosis / Q000187:drug effects*; D009865:Oocytes / Q000187:drug effects*; D011247:Pregnancy; D011359:Proestrus / Q000187:drug effects; D015053:Zygote / Q000187:drug effects
D001562:Benzimidazoles; D002219:Carbamates; D005659:Fungicides, Industrial; C006698:carbendazim