Models for studying prenatal
drug-induced
intrauterine growth retardation (IUGR) have, without exception, measured growth-related factors in the postimplantation embryo, fetus or neonate. Therefore, it is not known whether effects of
drug exposure on growth and metabolism begin early in the preimplantation embryo, or whether IUGR is exclusively a postimplantation phenomenon. The present study investigates whether
caffeine, a
drug known to induce a dose-dependent fetal IUGR, affects embryo development before and/or after implantation or is exclusively a fetal phenomenon. Preimplantation embryo assessment (with treatment from Days 2 to 4 of pregnancy) included
glucose utilization, cell number evaluation and stage of development (morula to hatched blastocyst); whereas, postimplantation embryo assessment (treatment from Days 2 to 10, 10.5 or 11 of pregnancy) included somite number evaluation and extent of neural tube closure, as seen using scanning electron microscopy. Comparing control preimplantation embryos with those exposed to 30 and 60 mg kg(-1)
caffeine did not reveal any effects of
caffeine exposure, as assessed on Day 5 of gestation. However, postimplantation embryo development assessed on Day 12 of gestation revealed that
caffeine exposure of 15 and 30 mg kg(-1) significantly reduced, at both dosage levels, somite number and the extent of neural tube closure. In addition, comparisons of control and experimental groups revealed that in the high-dose
caffeine group the forebrain cavity was significantly enlarged and bounded by a reduced, irregularly aligned neuroepithelium. The findings suggest that IUGR is a phenomenon first identifiable during late postimplantation embryogenesis and continues in fetal life.