Microphysiological systems of the placental barrier

Arumugasaamy, Navein; Rock, Kylie D.; Kuo, Che-Ying; Bale, Tracy L.; Fisher, John P.

doi:10.1016/j.addr.2020.08.010

Cited by 47 publications

(33 citation statements)

References 144 publications

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“…Results showed that Ti 3 C 2 nanosheet exposure increased trophoblast proliferation, combined with decreased endothelial cell migration in placentae, which may affect placental vascular maturation. Another major function of syncytiotrophoblast is to produce placental hormones to perform multiple functions of placenta and foetus development [ 48 ]. As a pregnancy-specific hormone produced by the syncytiotrophoblast, high or low hCG concentration is a marker of subsequent clinical manifestation of preeclampsia [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Exposure to two-dimensional ultrathin Ti3C2 (MXene) nanosheets during early pregnancy impairs neurodevelopment of offspring in mice

Wen

et al. 2022

J Nanobiotechnol

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Background Two-dimensional ultrathin Ti3C2 (MXene) nanosheets have been extensively explored for various biomedical applications. However, safety issues and the effects of Ti3C2 on human health remain poorly understood. Results To explore the influence on foetal or offspring after exposure to Ti3C2 nanosheets, we established a mouse model exposed to different doses of Ti3C2 nanosheets during early pregnancy in this study. We found that Ti3C2 nanosheets had negligible effect on the reproductive ability of maternal mice, including average pregnancy days, number of new-borns, and neonatal weight, etc. Unexpectedly, abnormal neurobehavior and pathological changes in the cerebral hippocampus and cortex in adult offspring were observed following Ti3C2 nanosheet treatment. In further studies, it was found that Ti3C2 exposure led to developmental and functional defects in the placenta, including reduced area of labyrinth, disordered secretion of placental hormones, and metabolic function derailment. The long-chain unsaturated fatty acids were significantly higher in the placenta after Ti3C2 exposure, especially docosahexaenoic acid (DHA) and linoleic acid. The metabolic pathway analysis showed that biosynthesis of unsaturated fatty acids was upregulated while linoleic acid metabolism was downregulated. Conclusions These developmental and functional defects, particularly metabolic function derailment in placenta may be the cause for the neuropathology in the offspring. This is the first report about the effects of Ti3C2 nanosheet exposure on pregnancy and offspring. The data provides a better understanding of Ti3C2 nanosheets safety. It is suggested that future studies should pay more attention to the long-term effects of nanomaterials exposure, including the health of offspring in adulthood, rather than only focus on short-term effects, such as pregnancy outcomes. Metabolomics could provide clues for finding the prevention targets of the biological negative effect of Ti3C2 nanosheets. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Exposure to two-dimensional ultrathin Ti3C2 (MXene) nanosheets during early pregnancy impairs neurodevelopment of offspring in mice

Wen

et al. 2022

J Nanobiotechnol

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“…Cellular Mn concentration does not increase over time, indicating that Mn homeostasis is maintained through effective import and export mechanisms within the cells. However, while the BeWo b30 trophoblast transfer model is recapitulating the most relevant barrier layer for nutrient transfer to the fetus, further studies should be performed using a co-culture model of trophoblasts and endothelial cells to understand the contribution of the endothelial barrier to maternal-fetal Mn transfer [ 15 , 27 , 57 ].…”

Section: Discussionmentioning

confidence: 99%

Differences and Interactions in Placental Manganese and Iron Transfer across an In Vitro Model of Human Villous Trophoblasts

Michaelis

Aengenheister

Tuchtenhagen

et al. 2022

IJMS

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Manganese (Mn) as well as iron (Fe) are essential trace elements (TE) important for the maintenance of physiological functions including fetal development. However, in the case of Mn, evidence suggests that excess levels of intrauterine Mn are associated with adverse pregnancy outcomes. Although Mn is known to cross the placenta, the fundamentals of Mn transfer kinetics and mechanisms are largely unknown. Moreover, exposure to combinations of TEs should be considered in mechanistic transfer studies, in particular for TEs expected to share similar transfer pathways. Here, we performed a mechanistic in vitro study on the placental transfer of Mn across a BeWo b30 trophoblast layer. Our data revealed distinct differences in the placental transfer of Mn and Fe. While placental permeability to Fe showed a clear inverse dose-dependency, Mn transfer was largely independent of the applied doses. Concurrent exposure of Mn and Fe revealed transfer interactions of Fe and Mn, indicating that they share common transfer mechanisms. In general, mRNA and protein expression of discussed transporters like DMT1, TfR, or FPN were only marginally altered in BeWo cells despite the different exposure scenarios highlighting that Mn transfer across the trophoblast layer likely involves a combination of active and passive transport processes.

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“…Though it is widely known that placental coordination is maintained by signals from both maternal and fetal circulation, an understanding of the detailed mechanisms is still elementary. [ 3 ] Placental phenotypic changes are also regulated by these signals. For instance, insufficient vascular endothelial growth factor (VEGF) or placental growth factor in maternal circulation can cause poor endothelial regulation and placental dysfunction or insufficiency.…”

Section: Introductionmentioning

confidence: 99%

Perspectives on the Technological Aspects and Biomedical Applications of Virus‐Like Particles/Nanoparticles in Reproductive Biology: Insights on the Medicinal and Toxicological Outlook

Chandrasekar

Singh

Maharjan

et al. 2022

Advanced NanoBiomed Research

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Increasing data on the infection indicate that maternal infections are severe. Under the realms of vaccine development, virus‐like particles (VLP)/nanoparticles (NPs) hold the promise of targeted control of therapeutics transfer across the placental barrier with the potential to trigger innate immune responses. Though the placenta is known to act as a barrier against exogenous materials, viruses exploit the transport systems and overcome the barrier properties. VLPs can be strategically designed to obtain the necessary mechanisms for navigation across the placenta and immune response. However, several knowledge gaps on the chemical, viral transmission strategies and the host defense response exist owing to the highly dynamic etiology of the placental barrier. This further complicates the toxicological analysis of the developed therapeutics. Herein, placental physiology and functions are discussed in significance with chemical toxicology, viral infections, and the host defense. Further, the promising applications of VLPs and perspective on their design to overcome the placental gatekeeper to gain the necessary immune response or therapy are provided. Finally, a holistic approach to various bioengineering models for studying chemical toxicants, viral infections, and effects of VLPs is provided to facilitate better translation of these VLPs to clinical applications.

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Microphysiological systems of the placental barrier

Cited by 47 publications

References 144 publications

Exposure to two-dimensional ultrathin Ti3C2 (MXene) nanosheets during early pregnancy impairs neurodevelopment of offspring in mice

Exposure to two-dimensional ultrathin Ti3C2 (MXene) nanosheets during early pregnancy impairs neurodevelopment of offspring in mice

Differences and Interactions in Placental Manganese and Iron Transfer across an In Vitro Model of Human Villous Trophoblasts

Perspectives on the Technological Aspects and Biomedical Applications of Virus‐Like Particles/Nanoparticles in Reproductive Biology: Insights on the Medicinal and Toxicological Outlook

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