Understanding Factors Influencing the Placenta's Protection During Pregnancy
DERT Success Story
Lauren Aleksunes, Pharm.D., Ph.D., D.A.B.T.
During pregnancy, mother’s-to-be have heightened awareness and concern about their exposure to environmental chemicals and use of pharmaceutical drugs. Mounting evidence suggests pregnancy is a crucial window of susceptibility, presenting the possibility of lifelong impacts for expectant mothers, their children, and future generations.
While working as a pharmacist, Lauren Aleksunes, Pharm.D., Ph.D., D.A.B.T., frequently received questions from expectant mothers about what prescription medications or personal care products were safe for their babies. Her work as a pharmacist coincided with her research training in toxicology at a time when many new specialized proteins were being discovered in the human body. These proteins, called transport proteins, are involved in moving materials in and out of cells. Aleksunes became interested in exploring how transport proteins really worked, and how environmental chemicals or pharmaceuticals pass between a pregnant woman and her baby.
Studying the protective functions of specialized transport proteins
One of the key cell transport proteins involved in moving chemicals and pharmaceuticals out of the body for excretion is the breast cancer resistance protein (BCRP). Due to its role in diverting chemicals for excretion, it is not surprising that BCRP is found in organs like the liver and kidneys. Interestingly, this protein is also found in high levels in the placenta. Aleksunes hypothesized that BCRP must not only function to remove potentially harmful chemicals out of the body, but that it also acts as a protective barrier during fetal development.
In 2012, Aleksunes received the NIEHS Outstanding New Environmental Scientist (ONES) award to study how placental BCRP may prevent environmental contaminants or pharmaceuticals from reaching the developing fetus during pregnancy. She and her team at the Environmental and Occupational Health Sciences Institute at Rutgers University have found that rather than acting as a strict barrier, BCRP acts more like a revolving door. It kicks the chemical right back out into the mother’s circulation to prevent chemicals from moving across the placenta towards the developing baby.
Given these intriguing research findings, Aleksunes believes that the BCRP could potentially broaden the range of pharmaceutical treatment options available for pregnant women, particularly those with ongoing diseases or those that arise during pregnancy such as gestational diabetes. At one point, a common oral medication used to treat type II diabetes was considered unsafe during pregnancy. However, researchers have found that BCRP prevents these medications from passing through the placenta and reaching the developing baby.
When transporters don’t work: Understanding factors that decrease protection
Aleksunes is also interested in understanding what happens to the developing fetus when BCRP does not function properly, and what factors alter the function of BCRP. The first scenario involves genetics. Like all proteins, BCRP is coded for by genes, and any variation between individuals in genetic make-up could increase or decrease the amount of BCRP expressed in the placenta. The second scenario involves the presence of certain environmental chemicals or pharmaceuticals in the body that might prevent BCRP from functioning properly. “These are all factors that can potentially influence the movement of chemicals from mom to baby,” Aleksunes said. “If there is less BCRP or if BCRP is not functioning, the baby could be exposed to higher levels of the chemical or drug than normal, which could be harmful for their development.” Aleksunes and her research team have also investigated how the combination of dietary components and an individual’s genetics may influence how well BCRP can work in the placenta.
Aleksunes has been exploring how other factors influence BCRP function as well. She and her team have been working collaboratively with investigators at Hackensack University to study how changes in oxygen levels might alter BCRP expression. Oxygen levels in the placenta can be associated with the altitude, or elevation, where a person lives. “Our first evidence that lower oxygen levels decreases the expression of BCRP was observed in cell culture studies,” Aleksunes said. “Recently, we were able to study these effects in human placentas.” In this study, she and her research team measured levels of BCRP in placental samples from healthy women who lived 2 miles above sea level compared to samples from women who lived just 1 mile above sea level during pregnancy.
The results from this study, recently published in Placenta, showed that women who lived at the higher elevation for the duration of their otherwise healthy pregnancy had fewer BCRP transporters in their placenta than women who lived at the lower elevation. “Having less BCRP may change the amount of chemicals a baby is exposed to during development, which is important to consider for both environmental exposures or for drug treatments,” Aleksunes noted. “Moving forward, we’re interested in following mothers and their children to determine if cord blood levels of chemicals or pharmaceuticals are associated with the differences in placental BCRP levels due to genetic factors, chemicals consumed in their diet, or external factors such as living at higher or lower elevations during pregnancy.”
Related Links and Publications:
Francois LN, Gorczyca L, Du J, Bircsak KM, Yen E, Wen X, Tu M-J, Yu A-M, Illsley NP, Zamudio S, Aleksunes LM. 2017. Down-regulation of the placental BCRP/ABCG2 transporter in response to hypoxia signaling. Placenta. In Press. doi: 10.1016/j.placenta.2017.01.125.
Bircsak KM, Gupta V, Yuen PY, Gorczyca L, Weinberger BI, Vetrano AM, Aleksunes LM. 2016. Genetic and dietary regulation of glyburide efflux by the human placental breast cancer resistance protein transporter. J Pharmacol Exp Ther 357(1):103-13. 10.1124/jpet.115.230185.