Effects of lindane on oocyte maturation and preimplantation embryonic development in the mouse

Abstract

Lindane, an organochlorine insecticide, is suspected of preimplantation embryonic toxicity based on in vitro experiments with bovine and murine embryos. To verify this hypothesis in vivo we tested lindane for developmental alterations during early embryonic cleavage in the mouse. Two treatment schedules were tested: three daily doses of 15 or 25 mg/kg b.w. lindane were orally administered to female mice either before mating or immediately after mating. Morphologic alterations (lysis or fragmentation of blastomeres, developmental arrest) of two-cell embryos and morulae were evaluated by inverted microscopy. In addition, cytologic abnormalities and cell proliferation delay, possibly induced during the first four cleavage cycles, were evaluated by fluorescent microscope analysis of the number and morphology of blastomere nuclei. A statistically significant increase of degenerating two-cell embryos was induced by exposure of preovulatory oocytes to the highest tested lindane dose. Early cleavage embryos exposed to the same dose showed a lower average number of blastomeres per morula, as well as a 40% reduction of the mitotic index with respect to matched controls. However, mean values in individual litters were variable and litter analysis did not show a lindane-related effect. One possible mechanism for the observed effects could be the recently demonstrated inhibitory action of lindane on gap junction-mediated cell communication between oocyte and cumulus cells. A comparison between human exposure levels and experimental doses based on measured and predicted blood concentrations suggests that there are ample margins of safety for human embryonic development at the present exposure levels.