Abstract

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.

Highlights

  • Per- and polyfluoroalkyl substances (PFAS) are synthetic carbon fluorine compounds used in industry and commerce since the 1940s [1]

  • In the first trimester villous placenta, both tropomyosin sensitive receptor kinase B (TrkB) and p75NTR staining were most pronounced in the STB and cytotrophoblast cells (CTBs) (Figure 1A)

  • TrkB and p75NTR receptors were primarily observed in the placental villous stroma distinguished it from the first trimester placenta (Figure 1B)

Read more

Summary

Introduction

Per- and polyfluoroalkyl substances (PFAS) are synthetic carbon fluorine compounds used in industry and commerce since the 1940s [1]. Previous studies estimate over 95% of Americans to have detectable levels of PFAS in their blood, but certain communities face disproportionate exposure risk [7,8,9]. One such affected population is in Pittsboro, North Carolina, where sum PFAS concentrations up to 1,076 ng/L and 270.8 ng/L were measured at drinking water intakes and in finished household drinking water, respectively.. One such affected population is in Pittsboro, North Carolina, where sum PFAS concentrations up to 1,076 ng/L and 270.8 ng/L were measured at drinking water intakes and in finished household drinking water, respectively.1 These numbers are over 30 times higher than those in the neighboring city of Durham and are strikingly higher than surrounding cities.. This study aims to characterize placental BDNF signaling and investigate whether PFAS exposure disrupts the signaling pathway in placental trophoblast cells

Objectives
Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call