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In a previous study oral administration of a commercial PCB mixture (Aroclor 1,260) to female rabbits (4 mg/kg b.wt. for 14 weeks) resulted in a significant accumulation of PCBs in 6-d-old blastocysts and increased preimplantation embryo mortality (1). In the present study, the direct toxicity of PCBs on preimplantation rabbit embryos was investigated during in vitro culture. One-day-old cleavage stages and 3-d-old rabbit morulae were cultured in BSM II medium supplemented with 1.5% BSA in a reduced oxygen concentration of 5% O2. They were exposed to 50, 5, or 0.5 microgram Aroclor 1,260/mL culture medium for 24 h. PCB (50 micrograms) led to a complete degeneration of the exposed embryos. Following exposure to 5 micrograms only 16% of the morulae developed into blastocysts. The others were either arrested in the morulae stage or were degenerated. Cell proliferation of the nondegenerated embryos was approximately 20% of that of corresponding control embryos. Compared with nonexposed controls, addition of 0.5 microgram PCB/mL showed either no or only a slight impairment of development. Preliminary embryo transfer experiments showed that morulae exposed to 5 micrograms PCB with clear signs of degeneration after 24 h in vitro culture were able to implant. Aroclor 1,260 is embryotoxic in a dose-dependent manner in cultured rabbit preimplantation embryos.

The commercial polychlorinated biphenyl (PCB) formulation Aroclor 1260 (4 mg/kg body weight), technical grade dichlorodiphenyltrichloroethane (DDT; 3 mg) and Lindane (gamma-hexachlorocyclohexane; 0.8 mg) were administered orally, either separately or in combination, to sexually mature female rabbits three times per week for 12-15 weeks. Oviductal and uterine luminal fluid, cleavage stage embryos (day 1 post coitum), blastocysts (day 6), fetuses, exocoelic fluid and placentae (day 11) were analysed, firstly for chlorinated hydrocarbon residues, and secondly for embryonic and fetal development. The doses applied were well tolerated by the treated animals. PCB and DDT accumulated in uterine secretions (day 6) but not in oviductal luminal fluid (day 1). Both chlorinated hydrocarbons were found in preimplantation blastocysts. Residues in day 11 fetuses were 16- (DDT) or 18-fold (PCB) higher than in day 6 blastocysts. Significant amounts were also detected in placental tissue and in exocoelic fluid. A specific accumulation of the highly chlorinated biphenyl congener no. 180 was noted in fetuses, placentae and exocoelic fluid. The clear accumulation of the chlorinated hydrocarbon compounds in luminal fluid and embryonic tissue is contrasted by rather weak effects on fertility. No statistically significant differences between treated animals and controls were observed for fertilization rate and pre- and post-implantation (up to day 11 post coitum) losses. However, in females exposed to PCB, a 20% higher loss of blastocysts was noticed, as compared with controls (P > 0.05). This effect was shown on day 6 of embryonic development and may be due to the embryotoxic activities of PCB.

The female rabbit was used to study (i) accumulation of lipophilic chlorinated hydrocarbons in genital tract tissues and (ii) subsequent morphological and functional effects after long-term low-dose exposure. Polychlorinated biphenyl (PCB), 1,1-di(p-chlorophenyl)-2,2,2-trichloroethane (DDT) and gamma-hexachlorocyclohexane (gamma-HCH) (dosages: 4, 3 and 0.8 mg per kg body weight, respectively) and a combination of these three components (and dosages) were administered to sexually mature rabbits over a period of 12-15 weeks. The animals were killed shortly before and at various times after ovulation. Accumulation of chlorinated hydrocarbons was high in ovarian, oviductal and uterine tissues, in follicular fluid and clearly detectable in uterine secretions. In follicular fluid, the concentration and patterns of congeners and isomers of PCB and DDT were distinctly different from serum. DDT- and gamma-HCH-treated animals showed a significantly reduced ovulation rate (P < 0.002 and 0.05, respectively). During early pregnancy DDT decreased serum progesterone levels and changed the protein pattern of uterine secretion. Functional effects, however, were much less expressed compared with the highly significant accumulation of the persistent organochlorines in the genital tract.