Preimplantation mouse embryo development as a target of the pesticide methoxychlor

Effects of methoxychlor (MXC) and estradiol-17beta (E) were studied in mouse preimplantation embryos. Pregnant mice received s.c. injections of sesame oil only, 10 mug E, or 0.5 mg purified (95%) MXC on Days 2-4 of pregnancy (plug = Day 1). Another group received a single dose of 2.5 mug E on Day 2 only. Based on the average weight of pregnant females, 10 mug of estradiol was equivalent to 0.33 mg/kg of bw, 2.5 mug of estradiol was equivalent to 0.082 mg/kg of bw, and the 0.5-mg dose of MXC was equivalent to 16.5 mg/kg of bw. All embryos were collected for analyses on Day 4. MXC and both estradiol-17beta doses suppressed embryonic development to blastocyst, decreased embryo cell numbers, and caused abnormal blastocyst formation. The high estradiol-17beta dose significantly increased the percent degenerating embryos and caused a tube-locking effect, with retention of embryos in the oviduct. In contrast to estradiol-17beta, MXC at the dose used in this study did not alter tubal transport of embryos. Also in contrast to estradiol-17beta, MXC increased the percentage of nuclear fragmentation and micronuclei. In preimplantation embryos, MXC and estradiol-17beta both suppressed embryo development. MXC effects were, however, different from those of estradiol-17beta, indicating a difference in mechanism of action, possibly due to cytotoxicity and induction of apoptosis. (C) 2002 Elsevier Science Inc. All rights reserved.