Bisphenol A: multisystem effects
September 23, 2010 Leave a comment
Are endocrine disruptors stealing our future?
Endocrine-disrupting compounds are chemicals in the environment—usually compounds that we have introduced—that can alter normal hormone signaling processes. Often, exposure to these compounds has little immediate effect in adult animals, but it can have big effects on organisms during sensitive developmental periods, like embryogenesis. During embryonic development in vertebrates, steroid hormones govern many processes, and the fetal hormone environment is usually carefully calibrated to ensure that these processes go forward normally.
Tiny amounts, big changes
But many compounds disrupt these processes, knocking them off track and resulting in development that is unusual or abnormal. For example, male alligators exposed in the egg to these compounds—which often persist in fatty tissues or yolk—emerge with serious penile abnormalities that can affect their ability to reproduce. The banned pesticide DDT is probably one of the best-known of these compounds, and exposure to it or its metabolites has been shown to disrupt hormone signaling to the point of altering sex development completely.
When we think of hormones, we often think of puberty, the time when hormones seem to govern our every move. When we think of estrogen, we probably think “female” because estrogen has historically been considered the “female” hormone. What you might not know is that estrogen, which is made in the ovaries, is also made in our brains during embryonic development. In mammals, appropriate male development appears to require neural estrogen synthesis. When estrogen synthesis in embryonic mammals is blocked, the males that develop do not exhibit typical male behaviors when they reach reproductive maturity.
Bisphenol A: ubiquitous chemical
Among the compounds that have been identified as endocrine disruptors is bisphenol A (BPA). In the United States, we produce about 2 billion pounds of BPA a year. Previous studies have demonstrated that BPA can disrupt thyroid signaling to the point of affecting the thyroid’s role in appropriate brain development. In addition, BPA has been linked to feminization of reptiles. Some scientists were aware of BPA’s hormone-activity potential as far back as the early twentieth century.
But because no one took that knowledge or its potential seriously—the field of endocrine disruptors is relatively young—BPA has found its way into almost every aspect of our lives. It is in the dental sealants we put on our teeth to keep the cavities at bay. It is in the lining that coats the insides of food cans to keep the metal from rusting. It is in the hard plastic that we use for baby bottles and teething rings. And it can leach from these products into the food that we eat. BPA is found at high levels in some pregnant women, and it appears to accumulate in higher concentrations around the umbilical cord and in the fetal amniotic fluid.
Work from Yale and from researchers in Japan also points to some potentially serious effects on the brain. Part of the role of estrogen in brain development is facilitating synaptic connections in a crucial brain area called the hippocampus. The hippocampus is the center where neurons organize that will later be activated to produce sex-appropriate activity in vertebrates. It is also the area of the brain involved in the formation and retention of memory.
The researchers found that small doses of BPA—doses that fall within EPA-approved levels for exposure—can inhibit hippocampal synaptic formation in rats, counteracting the effect of estrogen. That BPA is an estrogen inhibitor could be serious for our brains if the results translate into human effects. As we age and our endogenous estrogen levels decrease, for example, the hippocampus suffers and our memory does, too. If BPA sets this process in motion even earlier, hippocampal—and thus, memory—decline may occur even earlier.
Rodents, monkeys, and people–oh, my
A recent report in Environmental Health Perspectives concludes that rodents, rhesus monkeys, and people all exhibit similar pharmacokinetics with BPA and that exposures may be far greater than previously calculated. Other recent studies suggest effects on sugar metabolism related to diabetes, an association with polycystic ovarian syndrome in rats, and a relationship to the development of asthma in a mouse model.