In an article published on January 22, 2017 in the peer-reviewed journal Environmental Science & Technology, Jiaying Liu and colleagues from the Faculty of Medicine and Dentistry, University of Alberta, Canada, report on the content of several bisphenol A (BPA, CAS 80-05-7) alternatives, as well as BPA metabolites, in the blood of pregnant women and the cord blood of their newborns. The measurements were done for 61 pairs of maternal and fetal cord sera obtained from Chinese participants.
The scientists analyzed three BPA alternatives, namely bisphenol AF (BPAF, CAS 1478-61-1), bisphenol B (BPB, CAS 77-40-7), and bisphenol S (BPS, CAS 80-09-1). BPAF and BPB were not detected, and BPS was detected at low concentrations and low frequency (4 and 7 cases for maternal and fetal cord sera, respectively). This dataset, although limited, demonstrated that 1) BPS can pass the placenta and accumulate in fetal blood, and 2) higher maternal concentrations may result in higher fetal BPS levels. The authors suggested that one implication of these results is that future toxicology or epidemiology studies should consider co-exposure of BPA and the chemicals used as its alternatives.
To profile BPA metabolites, the scientists quantified BPA-glucuronide, BPA-sulfate, and BPA-bissulfate, from which only the first two were detectable. The lack of BPA-bissulfate detection was likely due to the limitations of the analytical method. No gender differences in BPA-sulfate and BPA-glucuronide levels in fetal cord serum were observed between male and female newborns.
Cord sera contained significantly higher concentrations of total BPA metabolites compared to maternal sera. This indicates that BPA metabolites could be either formed in the fetus or cleared more slowly from the fetoplacental compartment.
In both maternal and cord sera, BPA-sulfate was found to be the dominant metabolite, showing 2-3 times higher concentrations compared to BPA-glucuronide. These findings agree with the 2013 study by Gerona and colleagues, who measured BPA metabolites in the cord blood of mid-gestation fetuses in California (FPF reported). Moreover, the proportion of BPA-sulfate increased with total BPA.
The study by Liu and colleagues adds to the efforts on evaluating early-life exposure and risks of BPA. In 2006, Cheri Stowell and colleagues from Indiana University, U.S., showed that BPA-sulfate can be deconjugated by estrone sulfatase, particularly arylsulfatase C. This enzyme is highly expressed in estrogen-responsive tissues, where it deconjugates sulfated estrogens delivered with the blood stream. Following this, free estrogens are taken up by the cells. Similar mechanisms could operate with BPA-sulfate as well. Importantly, the expression of arylsulfatase C in human fetuses starts early on in the ontogeny. Similarly, BPA-glucuronide can be deconjunated by glucuronidases. These enzymes are also expressed in the fetus, but even higher in placenta. The conjugation-deconjugation pathways and their significance for fetal exposure to BPA have been discussed in a 2009 commentary by Gary Ginsberg and Deborah Rice. Essentially, the continuous deconjugation of BPA metabolites appears to significantly contribute to the exposure of the fetus to free BPA.
Emma Davies (February 2, 2017). “Common BPA alternative, BPS, crosses into placenta.” Chemical Watch
Liu, J., et al. (2017). “Bisphenol A metabolites and bisphenol S in paired maternal and cord serum.” Environmental Science & Technology (published online January 22, 2017).
Gerona, R., et al. (2013). “Bisphenol-A (BPA), BPA glucuronide, and BPA sulfate in midgestation umbilical cord serum in a Northern and Central California population.” Environmental Science & Technology 47:12477-12485.
Ginsberg, G., and Rice, D. (2009). “Does rapid metabolism ensure negligible risk from bisphenol A?” Environmental Health Perspectives 117:1639-1643.
Stowell, C., et al. (2006). “A role for sulfation-desulfation in the uptake of bisphenol A into breast tumor cells.” Chemistry & Biology 13:891-897.