Toxicological mechanisms of implantation failure

Implantation in mammals requires the successful completion of a series of integrated phenomena, including uterine preparation, synchronized embryo transport, embryonic attachment, uterine transformation, placental development, and the requisite hormonal milieu to support each step. Potential for toxic interference with early pregnancy exists at several points in this course of events via a variety of anatomical and physiological sites. An improved understanding of the mechanisms of implantation failure due to toxic insult is necessary in order to assess risks of reproductive toxicants to the human female population. As an approach to providing such information, a panel of tests has been assembled and developed to probe the mechanisms by which chemicals affect fertility in rodents. These assessments are performed only if adverse effects on litter size or pregnancy are evident from previous reproductive studies. The evaluation of methoxychlor, a weakly estrogenic pesticide, has served to partially validate this panel. The early pregnancy protocol provides dose-response information on the effects of short-term exposure of animals to compounds during early pregnancy. The pre- vs postimplantation protocol assesses the differential effects of such chemicals on the physiological events unique to the periods immediately preceding and following implantation. The decidual cell response technique can distinguish embryotoxicity from direct effects of toxicants on uterine or other physiological functions. Embryo transport rate analysis evaluates the potential for early embryonic loss via accelerated or retarded arrival of embryos into the uterus. The panel thus permits the determination of the site or sites of toxic insult and the mechanisms by which environmental toxicants may compromise fertility following short-term exposure during early pregnancy.