Wreaking Reproductive Havoc One Chemical at a Time
In the 1930s, biochemist Edward Charles Dodds hoped to find synthetic estrogens that could treat gynecological ailments caused by hormone deficiencies. In 1936, Dodds identified one candidate that stimulated the female reproductive system in rats whose ovaries had been removed. But the estrogenic activity of the compound, bisphenol A, paled next to the much stronger estrogen he would soon develop himself: diethylstilbestrol (DES). Dodds had noticed estrogen’s similarity to cancer-causing substances in early studies, but assumed that any drugs would be used only as short-term therapies, so the cancer risk would be small. He never expected DES or any other estrogens to be given to healthy women. Yet some 4 million expectant mothers received DES to prevent miscarriage before physicians realized they’d made a terrible mistake. DES greatly increased the risk of rare vaginal and cervical cancers in exposed daughters. Sons had a higher risk of testicular growths. Bisphenol A (BPA), unlike DES, remained obscure until the 1950s, when chemists tapped it to make polycarbonate plastics and epoxy resins. BPA now tops the list of high-volume chemicals, and is found in numerous consumer products, including water bottles, food packaging containers and can linings, and thermal paper products like cash receipts and boarding passes (Fig 1). And because it can leach out of products, it’s been detected in the urine of nearly every person tested. It’s also been found in breast milk, follicular and amniotic fluid, cord blood, placental tissue, fetal livers, and the blood of pregnant women. Hundreds of studies have associated the BPA levels found in most of us with reproductive disorders, cancers, obesity, and other adverse effects in both animals and humans. Although chemical manufacturers with a stake in the $16 billion BPA market continue to question this evidence, they’ve responded to safety concerns by offering BPA-free alternatives. But as a recent study in PLOS Genetics [1] shows, the new versions seem an awful lot like the original. When one chemical comes under scrutiny, manufacturers often substitute compounds with similar structures to save time and money. But similar structures often cause similar problems. And that’s exactly what the PLOS Genetics authors found. Thinking BPA’s replacement, bisphenol S (BPS), might target the same pathways, Patrick Allard and his colleagues at the University of California at Los Angeles compared the effects of both substances using the roundworm Caenorhabditis elegans, a favorite model for working out the genetics of meiosis, the process that creates sperm and oocytes. The worms did not fare well. BPS, like BPA, wreaked havoc with their germ cells. Both compounds interfered with DNA damage repair as genetic material was exchanged during meiosis. That in turn triggered the death of developing germline cells and lowered fertility by producing fewer viable embryos. But, surprisingly, the authors say, the two bisphenols gummed up the works through somewhat different molecular steps. That means simultaneous exposure to BPA and BPS could potentially cause even more reproductive harm. Future studies will need to confirm this possibility, but it’s an unsettling