Bisphenol A (BPA) is a synthetic industrial chemical found in many household goods and throughout polluted environments. In many animals, BPA can disrupt hormone signaling and even reproductive function, and this raises a concern that ubiquitous BPA exposure is negatively affecting the health of entire ecosystems and human populations. There is therefore much interest in understanding how BPA might affect humans and other animals at different levels of chronic or acute exposure.

Exposure to BPA in utero is known to affect reproductive function in developing mice, and recent studies have now shown that it can alter reproductive function for up to three generations (Toxicol. Appl. Pharmacol. 284, 354–362; 2015). Researchers at the University of Illinois administered different dosages of BPA or a control substance to pregnant mice and then monitored female offspring in three subsequent generations for an array of developmental and reproductive parameters. The researchers administered the BPA orally, with the consideration that most humans are exposed to BPA through diet.

Immediate differences were apparent in the first generation of mice, which were exposed in utero, and some of these corroborated previous research: at the age of nine months these mice showed higher weights and lower indices for fertility and gestation. The most novel findings, however, arose as some effects persisted into the second and third generations of mice. At the age of nine months, mice of the second generation showed a markedly lower gestational index, and mice of the second and third generations showed lower fertility indices. Some effects even appeared unexpectedly in just the third generation. Mice whose grandmothers were exposed to BPA in utero showed delays in sexual development that were not seen in their mothers or grandmothers.

Some of the most pronounced effects were measured in mice whose progenitors received the lowest dose of BPA. Jodi Flaws, who led this study, acknowledged that this might seem counterintuitive, “but with endocrine-disrupting chemicals, it's sometimes the low doses that cause the most profound effects,” she noted.

This particular finding emphasizes the importance of investigating chronic exposure to low levels of BPA. Research suggests that BPA has a relatively short half-life and is quickly metabolized in humans, but its pervasive presence can lead to near constant exposure for many people. Some studies have even found BPA in human ovarian follicular fluid, placental tissue and fetal plasma. As BPA percolates through foods, materials and environments it will be important to understand its lasting legacy in affected organisms and populations.