Pregnancy is a new window of susceptibility for bisphenol a exposure.

Bisphenol A (BPA) is a well-known synthetic compound that is widely studied for its various toxic and endocrine disrupting properties. In our industrialized world, BPA is ubiquitous; it is present in our food, water, air, and clothes. At relevant levels, BPA is involved or associated with an array of diseases related to reproduction, development, metabolism, cancers, immunity, and inflammation (1, 2). Although several studies showed inconclusive or mixed results (3,–5), BPA showed toxic effects in many animal studies during certain windows of susceptibility (1). One such well-studied susceptibility window for BPA action is during early development. There is well-documented evidence in laboratory animals demonstrating that in utero exposure to BPA increases the risk of numerous adverse effects to the offspring (6). Consequently, the United States Food and Drug Administration (FDA) issued an assessment identifying BPA as a possible health risk to fetuses, infants, and children. The FDA, however, recently revised its assessment saying “FDA's current perspective, based on its most recent safety assessment, is that BPA is safe at the current levels occurring in foods” (7). Meanwhile, the FDA continues to review and monitor new scientific results on possible safety issues with the use of BPA. As the debate on the safety of BPA continues, an interesting new study published in this issue of Endocrinology identifies a possible new health concern for mothers (8). Alonso-Magdalena et al show that pregnancy is a critical window of susceptibility for BPA effects, potentially causing glucose intolerance and altered insulin sensitivity in mothers later in their lives (8). Their findings reveal that gestational BPA exposure has detrimental long-term effects in the glucose metabolism of the dams (8). In a series of well-designed experiments, they show that BPA exposure from days 9–16 of gestation caused hyperglycemia after 4 months and the condition deteriorated with time when compared with vehicle-treated controls and nonpregnant mice with a similar exposure. Further, these affected mice secreted less insulin due to impaired insulin production in the pancreatic β-cells, and Alonso-Magdalena et al (8) go on to explain the mechanism for decreased insulin production. They also show that these mice have significantly increased gonadal fat depot. This study is of immense importance because 1) it identifies a previously unknown effect of BPA on maternal health, and 2) it identifies pregnancy as a new window of susceptibility for the development of diabetes in mothers. Until recently, the prenatal and neonatal periods were thought to be most vulnerable to environmental exposures and investigations were focused on effects in offspring. It is well known that various adverse uterine environment causes hyperglycemia and insulin resistance in the offspring. Effects such as caloric restriction (9), low protein diet (10, 11), overnutrition (12), exposure to glucocorticoids (13), and BPA (14) are known to cause hyperglycemia and insulin resistance in offspring. However, this study has forced us to rethink and expand our attention to include the maternal wellbeing also. Effects of maternal BPA exposure in humans are not well understood. Several epidemiological studies have shown that parity is a risk for the development of type 2 diabetes in later life (15,–21); however, other studies have contradictory findings (22,–24). These conflicting findings have been suggested to be due to other confounding factors such as body weight, dietary habits, and socio-economic status (23). In the light of the new findings in mice, it is tempting to ask whether BPA is also a contributing factor in the development of type 2 diabetes in these women. Currently, we do not know whether BPA plays any role in the development of type 2 diabetes in women after pregnancy and further detailed investigations are needed. We need well-defined studies to correlate BPA levels during pregnancy in normal women and determine the odds of the development of type 2 diabetes in these women in subsequent years. We will need to gather this information in different ethnicities and geographical locations to arrive at a concrete conclusion. BPA is pervasive and its daily exposure is inevitable. Although the FDA considers that it is safe at current exposure levels in food, we still do not know many aspects of this compound. This study by Alonso-Magdalena and coworkers (8) shows that exposure levels alone can no longer be considered as the only criteria for toxicity studies, the timing of the exposure may be even more important. Even low levels of exposure that are currently considered “acceptable” may cause serious ill effects during certain vulnerable periods of life. Furthermore, the effects of exposure may not be immediate and may take months or years to develop. This study has identified pregnancy as a new window of susceptibility for BPA action. It is not known whether there are other such windows of susceptibility that could cause insulin resistance and hyperglycemia. We need to take into consideration not just the levels and duration of exposure but also when the exposure occurs. As with early development and pregnancy, are there other periods of vulnerability? Could exposure to BPA during puberty, menopause, or certain immunocompromised states have any health consequences? What levels of exposure, if any, are safe during these susceptibility periods? We do not know the answers to these questions. Hence, instead of downplaying the possible risks of BPA exposure, we must realize that we have a long way to go and many questions remain yet unanswered.