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Prenatal BPA induces nitrosative stress in mother, fetus
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Exposure to bisphenol A during pregnancy brings on nitrosative stress in both expecting mothers and fetuses, according to findings published in Endocrinology.
Observed increases in 3-nitrotyrosine (NY), a marker of nitrosative stress, in mothers and umbilical cord samples point to its potential utility as a biomarker for offspring health. Maternal samples also showed elevated palmitic acid, which positively correlated with NY.
“The current study provides first unequivocal evidence that developmental exposure to BPA can induce nitrosative stress, and that this effect is conserved across humans and two of the animal species studied,” the researchers wrote.
Almudena Veiga-Lopez, MD, of the University of Michigan, Ann Arbor, and colleagues from other institutions investigated the effects of gestational bisphenol A (BPA) on oxidative stress and free fatty acids (FFAs) in humans and animals.
“In assessing human risk posed by BPA, because sensitivity to BPA is likely to vary between species, causal studies in several species are needed,” the researchers wrote. “Furthermore, because route of administration, uptake, and metabolism of BPA are also likely to vary between species and from fetus to adult, it is important to relate internal levels in body fluids/tissues, as a reference point to assess human risk.”
The researchers recruited expecting mothers aged ≥18 years in their first trimester from the community surrounding the University of Michigan Von Voigtlander Women’s Hospital; the women conceived naturally without infertility treatment and had singleton pregnancies. Exclusions were made for gestational diabetes, preterm birth, preeclampsia or newborn abnormalities.
The investigators drew mothers’ blood by venipuncture during an initial study visit and, after delivery, collected blood samples from the cord, clamped proximal to the placenta; all samples were gathered and processed without contacting plastic to avoid BPA contamination.
Using first trimester maternal unconjugated BPA (uBPA) levels, maternal samples and pair-matched term umbilical cord were selected from women demonstrating low uBPA-exposure (n=12; 0.08 ng/mL ± 0.01 ng/mL) and high uBPA-exposure (n=12; 27.79 ng/mL ± 8.38 ng/mL). BPA glucuronide (BPA-G) was also calculated.
The scientists measured FFAs in plasma of human maternal samples and used isotope dilution liquid chromatography electrospray ionization tandem mass spectrometry to quantify protein-bound oxidized tyrosine moieties (3-nitrotyrosine [NY], 3-chlorotyrosine [ClY], and o, o’-dityrosine [DiY]).
All measurements were taken in sheep, rats and mice using appropriate methods.
The researchers used general linear models to analyze the impact of prenatal BPA (all three animal species) on FFA and oxidative stress variables, along with the relationship between BPA levels in maternal circulation during human pregnancies and FFA and oxidative stress variables.
Significantly, differences were seen in the levels of uBPA levels in maternal samples of low vs. high BPA exposures, as expected; this significance remained in BPA-G level comparison (P<.05). Further, maternal uBPA levels were significantly higher than term cord blood samples (P<.02). BPA-G in first trimester samples positively correlated with term cord samples (P<.05); the correlation was not seen for uBPA.
Palmitic acid was higher in the high BPA exposure group vs. low BPA exposure group (P=.012). Further, positive correlations were observed between uBPA and palmitic acid (P<.001) and between uBPA and total FFA (P <.001); this was not so for BPA-G.
A trend towards positive correlation was seen between palmitic acid and NY/tyrosine (P=.062).
“Overall, these findings are supportive of the potential use of maternal NY as a biomarker for future offspring health, although further studies are required to pinpoint the specific pathways by which this is programmed developmentally,” the researchers wrote.
Disclosure: The researchers report no relevant disclosures.
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