When it comes to the effects of prenatal chemical exposures, timing is everything. That is the consensus of a series of reviews and new research articles published in the April/May issue of Reproductive Toxicology. The special issue highlights exposures of developing fetuses to various chemicals and the possible impacts on adult diseases such as Parkinson's, obesity, heart disease, and cancer.
Compared with the gross fetal malformations from prenatal thalidomide exposure, the footprints left behind by most toxins are more subtle. For example, methylmercury exposure from fish consumed by mothers-to- be has neurotoxic effects at high levels and can cause low birth weight and other negative effects. Philippe Grandjean of the Harvard School of Public Health and the University of Southern Denmark reviews cases of the less obvious effects at even lower levels, using data from such far-flung sites as the Faroe Islands and New Zealand. Physical coordination and brain functions are "sensitive targets of methylmercury toxicity" even at lower levels of exposure, which are possibly culpable in attention deficit disorder and brain-function disabilities, writes Grandjean.
In another review, Gail S. Prins of the University of Illinois at Chicago and colleagues argue that exposure to estradiols in utero may be contributing to prostate cancer in humans. Extrapolating from studies of rats affected during the perinatal period, the authors add to the mix gene methylation, a cellularly inherited DNA alteration that may come from exposure to bisphenol A or other endocrine disrupters. The researchers emphasize how critical the period of fetal exposure is to later development and how it may lead to many adult diseases.
Other papers in the journal's special issue include new research from Theodore Slotkin and Frederic Seidler of Duke University Medical Center on the effects of fetal and prenatal exposure of rats to chlorpyrifos, a pesticide banned for termite control in 2005. Such organophosphates affect serotonin systems as they develop in the womb, ultimately affecting gender differentiation of the rats' brains during puberty.
Despite obvious shortcomings of rodent-to-human extrapolations, the research underscores the importance of the level of exposure and its timing. During the peak period of sexual differentiation (gestational days 17-20), male fetuses showed brain changes when their mothers were injected with 1 milligram of chlorpyrifos per kilogram body weight. Female rats responded only to doses five times as high during the same period.
Copyright 2007 American Chemical Society