The teratogenic effects of nicotine in vitro in rats: a light and electron microscope study

Cigarette smoking in pregnant women has been shown to lead to intrauterine growth retardation and fetal death, and possibly also to neural dysmorphology and long-term learning deficits in the offspring. Because the teratogenic agent in cigarette smoke remains controversial, the present study on rat embryos in culture examined specifically whether nicotine can cause neural dysmorphology and, hence, act as a nervous system teratogen. This in vitro study confirmed previous reports in utero that nicotine leads to growth retardation, and, in addition, demonstrated that development of the nervous system, particularly the forebrain, as well as the branchial arches was impaired, possibly leading to microcephaly and cleft palate respectively in term fetuses. Cellular disruption and necrosis occurred in the neuroepithelium and underlying mesenchyme, with the effect being dose dependent. Ultrastructurally, there was severe disruption of cell and organelle membranes, with many healthy cells containing engulfed, whole condensed or remnants of dead cells. This study demonstrates that nicotine acts as a nervous system teratogen leading to gross and cellular dysmorphology. Suggested mechanisms for nicotine action include the possibility that the highly lipid soluble teratogen may exert its effects directly on the membranes or indirectly through oxidative membrane damage.