The industrial chemical Bisphenol A (BPA) is an ingredient in dozens of everyday products -- baby and water bottles, sports equipment, medical and dental devices, dental filling sealants, CDs and DVDs, household electronics, eyeglass lenses, foundry castings and the lining of water pipes. Manufacturers worldwide use at least 3.6 billion kilograms (8 billion pounds) of BPA to make polycarbonate plastic and epoxy resins every year.
Over the past decade, studies have shown that BPA is widely present in the environment and in our bodies. BPA can be measured in human serum, urine, umbilical cord blood, amniotic fluid and placental tissue. Some studies have suggested that BPA may affect human reproductive and other systems by behaving like human hormones. Many countries, including the United States, Australia, Canada, New Zealand, the United Kingdom, Japan and those in the European Union, have banned the use of BPA in baby bottles and other polycarbonate items produced for babies and toddlers.
In response, manufacturers have introduced "BPA-free" products made with substitute chemicals. Bisphenol S (BPS) is one of the most widely used BPA replacements. A 2012 of urine samples taken in the United States, Japan, China and five other Asian countries confirmed that humans are widely exposed to BPS from drinking from containers or cans lined with the chemical or contamination through the water supply.
However, BPS may not be safer than BPA. Two recent studies have found that BPS is as hormonally active as BPA and, like BPA, it interferes with the endocrine (hormone) system in ways that may produce harmful effects, such as obesity, cancer and neurological disorders. In a paper published last month, we showed that both of these endocrine-disrupting chemicals alter normal development of the reproductive system.
Impacts on Reproductive Development
As endocrinologists concerned about public safety, we wanted to know whether BPS had effects similar to BPA during embryonic development of brain cells and genes that control puberty and fertility later in life. We chose to study the embryo because animals are particularly susceptible to toxins at this stage.
As our subjects, we used zebrafish because their embryos are transparent, making it possible to watch their cells and organs develop in real time. And the zebrafish genome has been sequenced, which allows us to study genes that are involved in reproduction.
To understand whether BPA and BPS affected normal development of our target genes and brain cells, we studied how exposure to low levels of each chemical affected embryos' survival, hatching rate and development of gonadotropin-releasing hormone (GnRH) neurons. These are the brain cells that control reproduction. We also measured their levels of reproduction-related genes during embryonic and early larval development.
In addition to looking for these effects, we wanted to understand the process through which BPA and BPS could be impacting development of embryos. Studies have shown that BPA mimics the actions of estrogen, but there is also evidence that it interferes with normal thyroid hormone signaling. Thyroid hormones play essential roles in regulating fetal brain development, so we wanted to know whether BPA and BPS also influence that hormonal pathway in a way that affects reproductive development.
We already know that BPA is widely present in the environment worldwide. It is released in two ways: directly from manufacturing waste, or through leaching from products containing BPA that are buried in landfills. Currently BPA can be found in river water at levels up to 21 micrograms per liter. Concentrations as low as 0.1 micrograms per liter can harm fish and other aquatic organisms over time.
In our study, we found that when zebrafish embryos were exposed to levels of BPA that can be detected in the environment during development, they hatched early and had increased numbers of GnRH neurons and reproduction-related genes expressed in their brains and pituitary glands. This indicates that BPA has significant effected the reproductive development. We also found that equally low levels of BPS produced similar effects.
BPA and BPS alter reproductive development in ways that we don't fully understand yet. Further work needs to be performed to understand how chronic exposure to low levels of the chemicals affects an organism’s development through its life.
Next we investigated whether BPA and BPS acted like other hormones in addition to estrogen. Hormones act like messengers in the body, delivering instructions to target cells. Those target cells have receptors -- areas that detect the hormone and allow it to bind to the target cell and trigger certain responses.
We wanted to compare BPA and BPS to estrogen, thyroid hormone and aromatase, an enzyme that influences sexual development by converting testosterone to estrogen. We used inhibitors for each of these substances -- chemicals that block the actions of estrogen and thyroid hormone at their receptors, and block the enzymatic activity of aromatase so that it is not functional.
If these inhibitors could also prevent BPA and BPS from their actions in cells, that would be further evidence that BPA and BPS behave like hormones in the body. When we combined these treatments with either BPA or BPS, they blocked those chemicals' stimulatory actions on many reproduction-related genes. By showing that the inhibitors for estrogen, thyroid hormone and aromatase blocked BPA and BPS from affecting target cells, we demonstrated that BPA and BPS behave like several different hormones.
Altogether, these data suggest that both BPA and BPS have the potential to impact development of the reproductive system. And although BPA is often referred to as a chemical that mimics estrogen, our findings indicate that both BPA and BPS affect a wider wider range of cellular processes.
The GnRH neurons and reproduction-related genes that we studied ultimately control development of testes and ovaries, puberty and fertility. Our work provides important supporting evidence that both BPA and BPS alter fundamental characteristics of the developing reproductive system in ways that could have later impacts on reproductive health. In sum, BPS is not necessarily a safer alternative to BPA.