Abstract:
Models for studying prenatal drug-inducedintrauterine growth retardation (IUGR) have, without exception, measuredgrowth-related factors in the postimplantation embryo, fetus or neonate.Therefore, it is not known whether effects of drug exposure on growth andmetabolism begin early in the preimplantation embryo, or whether IUGR isexclusively a postimplantation phenomenon. The present study investigateswhether caffeine, a drug known to induce a dose-dependent fetal IUGR, affectsembryo development before and/or after implantation or is exclusively afetal phenomenon. Preimplantation embryo assessment (with treatment from Days2 to 4 of pregnancy) included glucose utilization, cell number evaluation andstage of development (morula to hatched blastocyst); whereas, postimplantationembryo assessment (treatment from Days 2 to 10, 10.5 or 11 of pregnancy)included somite number evaluation and extent of neural tube closure, as seenusing scanning electron microscopy. Comparing control preimplantation embryoswith those exposed to 30 and 60 mg kg -1 caffeine did not reveal anyeffects of caffeine exposure, as assessed on Day 5 of gestation. However,postimplantation embryo development assessed on Day 12 of gestation revealedthat caffeine exposure of 15 and 30 mg kg -1 significantly reduced, atboth dosage levels, somite number and the extent of neural tube closure. Inaddition, comparisons of control and experimental groups revealed that in thehigh-dose caffeine group the forebrain cavity was significantly enlarged andbounded by a reduced, irregularly aligned neuroepithelium. The findingssuggest that IUGR is a phenomenon first identifiable during latepostimplantation embryogenesis and continues in fetal life.