Fertilization and early embryology: Effects of persistent chlorinated hydrocarbons on fertility and embryonic development in the rabbit

Abstract

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.

Hormonal control of arylhydrocarbon receptor (AhR) expression in the preimplantation rabbit uterus

“…Although the physiological ligand is still unknown, a variety of xenobiotic compounds, including polyhalogenated dibenzo-dioxins and structurally related molecules such as coplanar polychlorinated biphenyls (PCB), have been shown to bind to the AhR, thereby mediating their toxic, teratological and/or developmental effects (Peterson et al 1993). Exposure of rabbit and mice to PCB or dioxins significantly affected reproduction, resulting in, for example, reduced fertilization and implantation rates, impaired embryo growth and increased embryo mortality (Couture et al 1990;Kholkute et al 1994a, b;Seiler et al 1994;Lindenau and Fischer 1996;Küchenhoff et al 1999a).…”

Prenatal Exposure to the Pesticide Dieldrin or the GABA_A Receptor Antagonist Bicuculline Differentially Alters Expression of GABA_A Receptor Subunit mRNAs in Fetal Rat Brainstem

“…Prenatal or perinatal exposure to these neurotoxins should be of special concern, since they readily pass the placenta, and accumulate in uterine tissues and breast milk [Seiler et al, 1994]. Because of their ability to block the actions of GABA by binding to GABA A receptor/Clchannels, it is possible that organochlorine pesticides may interfere with development of the central nervous system.…”

An Overview of Some Reproductive Toxicology Studies Conducted At Health Canada

“…It should be noted that in the mouse, 100 ppb (0.1 1 gg/ml) of Aroclor-1254 inhibited fertilization of oocytes and embryonic development (Kholkute et al, 1994). Aroclor-1260 is also embryotoxic on day 6 in the rabbit (Seiler et al, 1994). In this study, PCB 138, 153, and 180 were measured in blastocysts and luminal fluid, with PCB 180 having the highest concentration (Seiler et al, 1994).…”