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The Peruvian Amazon is facing the highest known input of mercury pollution of any ecosystem globally. Intact forests located near artisanal gold mining are particularly at risk from this toxin.

BackgroundPer- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants that have become globally ubiquitous in humans and the environment. In utero PFAS exposure is associated with neurodevelopmental effects; however, the mechanism is poorly understood. Brain-derived neurotrophic factor (BDNF) signaling is critical to fetal neurodevelopment during pregnancy and maintains important regulatory roles later in life. This study aims to characterize placental BDNF signaling and investigate whether PFAS exposure disrupts the signaling pathway in placental trophoblast cells.MethodsThe expression and localization of BDNF receptors–p75NTR and TrkB–in first trimester and term human placentas and trophoblast cells were investigated by immunofluorescence staining. To assess the effects of PFAS exposure on the BDNF pathway, BeWo cells were treated with PFAS mixtures that mimicked blood levels in a highly exposed population and major PFAS compounds in the mixture at 0.01, 0.1, 1, and 10 µM concentrations. Changes in pro-BDNF levels and phosphorylation of TrkB receptors were examined by Western blot.ResultsIn first trimester human placentas, TrkB and p75NTR receptors were primarily localized to syncytiotrophoblast and cytotrophoblast cells. At term, TrkB and p75NTR receptors were primarily observed in the placental villous stroma. TrkB receptor staining in trophoblasts was reduced at term, while p75NTR receptor staining was negative. TrkB receptors were confined to the nuclear and perinuclear spaces, and phosphorylation occurred at the Tyr816 residue in BeWo cells. Exposure to PFOS, PFOA, PFBS, and the six-PFAS mixture did not significantly affect BDNF levels or activation (phosphorylation) of TrkB. Treating cells with 1 μM and 10 μM of PFNA resulted in increased TrkB phosphorylation compared to unexposed controls, but BDNF levels were unchanged.ConclusionsBDNF receptors are present in different regions of human placental villi, indicating diverse functions of BDNF signaling in placental development. Our findings suggest that the BDNF pathway in placental trophoblast cells is not disrupted by exposures to PFOS, PFOA, PFBS, and a PFAS mixture, but may be affected by PFNA exposures. Further investigation is needed on how PFAS affects other critical signaling pathways during fetal neurodevelopment.

Artisanal and small-scale gold mining (ASGM) is the largest global anthropogenic mercury (Hg) source and is widespread in the Peruvian Amazon. Consuming Hg-laden foods exposes people to this potent neurotoxin. While numerous studies have examined fish Hg content near ASGM, Hg accumulation in other commonly consumed animal-and plant-based foods from terrestrial environments is often overlooked. In this study, we aim to address understudied dietary Hg exposures. To understand Hg exposure from food staples in the Peruvian Amazon, we measured total and methyl Hg in local crops, fish, chicken meat, chicken feathers, and eggs from ASGM-impacted and upstream (reference) communities. Diet surveys were used to estimate probable weekly Hg intake from each food. Fish and chicken stable carbon and nitrogen isotope signatures were analyzed to evaluate trophic magnification. Though few crops exceeded food safety recommendations, rice methyl Hg proportions were high (84%). Trophic level was an expected key predictor of fish Hg content. 81% (17 of 21) of local carnivorous fish exceeded WHO and EPA recommendations. Compared to upstream communities, mining-impacted communities demonstrated elevated total Hg in crops (1.55 (interquartile ranges (IQR): 0.60–3.03) μ g kg ^−1 upstream versus 3.38 (IQR: 1.62–11.58) in mining areas), chicken meats (2.69 (IQR: BDL–9.96) μ g kg ^−1 versus 19.68 (IQR: 6.33–48.1)), and feathers (91.20 (IQR: 39.19–216.13) μ g kg ^−1 versus 329.99 (IQR: 173.22–464.99)). Chicken meats from mining areas exhibited over double the methyl Hg concentrations of those upstream. Methyl Hg fractions in chicken muscle tissue averaged 93%. Egg whites and livers exceeded Hg recommendations most frequently. Proximity to mining, but not trophic position, was a predictor of chicken Hg content. Our results demonstrate that terrestrial and aquatic foods can accumulate Hg from mining activity, introducing additional human Hg exposure routes. However, locally sourced carnivorous fish was the largest contributor to an estimated three-fold exceedance of the provisional tolerable weekly Hg intake.