Harmful Farming

This issue of PLoS Genetics contains the second of two important papers describing the high levels of meiotic failure caused by exposure of female mice to a chemical known as Bisphenol A (BPA) [1]. In the first article [2], Pat Hunt and her collaborators demonstrated high levels of meiotic failure in females exposed to BPA, suggesting that BPA exposure affects maturing oocytes. This conclusion has been recently buttressed by an in vitro study by Can et al. [3] that demonstrates microtubule and centrosome changes in mouse eggs exposed to BPA, leading to an increase in aneuploidy. The new study takes this matter alarmingly further by demonstrating high levels of meiotic disruption, including perturbed synapsis and a greatly altered distribution of recombination events, in oocytes of fetuses being carried by mothers exposed to BPA. Part of the importance of these twin findings is that they provide people studying mammalian meiosis with powerful new tools for the study of the control of meiotic progression, both during and after meiotic prophase. Understanding the mode of action of BPA during both periods of the meiotic process may provide key insights into the regulation of meiosis. But, perhaps more importantly, these observations represent the most convincing demonstration to date that environmental exposures may affect meiotic processes in mammals. Indeed, this discovery raises the troubling issue of whether or not this chemical, or other similar chemicals, pose a risk to meiotic fidelity in the human population, one that might increase the already high frequency of meiotic failures. As the authors point out, ‘‘We are exposed to BPA daily; it is a component of polycarbonate plastics, resins lining food/beverage containers, and additives in a variety of consumer products. More than 6 billion pounds are produced worldwide annually, and several studies have reported levels of BPA in human tissues in the parts per billion range.’’ Mammalian oocytes enter meiotic prophase in the fetal ovary, where synapsis and recombination occur. Alteration in the number or distribution of recombination sites is well-known to play a major role in the origin of meiotic aneuploidy, especially in younger mothers. Thus, the findings in mice that BPA interferes with these processes raise the disturbing possibility that the exposure of women to BPA today might not be manifest for another generation. It is reasonable to ask whether the potential risks of ubiquitous exposure to BPA are sufficient to warrant the regulation of human exposure or at least to call for well-designed human studies. Answering this question is not going to be easy for several reasons. First, when it comes to reproducing, we humans are terribly inefficient. No less than 15%–20% of human conceptions end in miscarriage, and an astonishing 50% of these are chromosomally abnormal. (Compare this to the common fruit fly, whose eggs are chromosomally normal in more than 99.9% of cases.) Against that sort of background of meiotic failure, it may be difficult indeed to identify any environmental component that influences the rate of nondisjunction. Another complication is that most chromosomally abnormal conceptions are lost before birth, so that studies of live births provide an infrequent and nonrepresentative sample of all aneuploid conceptions. Second, attempts to identify environmental factors associated with the frequency of chromosome errors have been almost uniformly negative [4]. Surveys of miscarriages in very different populations find little or no difference in the rates of trisomies, other than those that can be explained by differences in mean maternal age, suggesting that most environmental differences have at best a weak effect on the level of meiotic failure. Two major studies, one in New York City, which included many AfricanAmericans and Hispanics [5], and one in Hawaii, which included many people of Asian and Hawaiian descent [6], gave results that were extremely similar in all respects. We can conclude that high levels of aneuploidy are a fact of human life that is independent of race and socioeconomic status, factors usually associated with environmental differences. The high rate of chromosomal anomalies in our species seems to be built into our biology and is not usually the result of the accumulation of adverse events. Third, the strongest predictor of the frequency of meiotic error in oocytes is doi:10.1371/journal.pgen.0030006.g002