Maternal Engineered Nanomaterial Inhalation During Gestation Disrupts Vascular Kisspeptin Reactivity

Bowdridge, Elizabeth C.; Abukabda, Alaeddin B.; Engles, Kevin J; McBride, Carroll R.; Batchelor, Thomas P.; Goldsmith, William T.; Garner, Krista L; Friend, Sherri; Nurkiewicz, Timothy R.

doi:10.1093/toxsci/kfz064

“…The results of our current study also corroborate data from previous nanotoxicological investigations from our group and others that have shown reduced fetal weight, or restricted fetal growth, after chronic maternal inhalation of nano-titanium dioxide particles [39,52]. We have previously postulated that diminished fetal development after maternal nanoparticle exposure in our studies may be associated with indirect vascular de ciencies leading to uteroplacental ischemia in late-stages of pregnancy [39,53,54].…”

Section: Discussionsupporting

confidence: 91%

Nanopolystyrene translocation and fetal deposition after acute lung exposure during late-stage pregnancy

Fournier

¹

,

D’Errico

²

,

Adler

³

et al. 2020

Preprint

1

0

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Background: Plastic is everywhere. It is used in food packaging, storage containers, electronics, furniture, clothing, and common single-use disposable items. Microplastic and nanoplastic particulates are formed from bulk fragmentation and disintegration of plastic pollution. Plastic particulates have recently been detected in indoor air and remote atmospheric fallout. Due to their small size, microplastic and nanoplastic particulate in the atmosphere can be inhaled and may pose a risk for human health, specifically in susceptible populations. When inhaled, nanosized particles have been shown to translocate across pulmonary cell barriers to secondary organs, including the placenta. However, the potential for maternal-to-fetal translocation of nanosized-plastic particles and the impact of nanoplastic deposition or accumulation on fetal health remain unknown. In this study we investigated whether nanopolystyrene particles can cross the placental barrier and deposit in fetal tissues after maternal pulmonary exposure.Results: Pregnant Sprague Dawley rats were exposed to 20 nm rhodamine-labeled nanopolystyrene beads (2.64 x 1014 particles) via intratracheal instillation on gestational day (GD) 19. Twenty-four hours later on GD 20, maternal and fetal tissues were evaluated using fluorescent optical imaging. Fetal tissues were fixed for particle visualization with hyperspectral microscopy. Using isolated placental perfusion, a known concentration of nanopolystyrene was injected into the uterine artery. Maternal and fetal effluents were collected for 180 minutes and assessed for polystyrene particle concentration. Twenty-four hours after maternal exposure, fetal and placental weights were significantly lower (7% and 8%, respectively) compared with controls. Nanopolystyrene particles were detected in the maternal lung, heart, and spleen. Polystyrene nanoparticles were also observed in the placenta, fetal liver, lungs, heart, kidney, and brain suggesting maternal lung-to-fetal tissue nanoparticle translocation in late stage pregnancy.Conclusion: These studies confirm that maternal pulmonary exposure to nanopolystyrene results in the translocation of plastic particles to placental and fetal tissues and renders the fetoplacental unit vulnerable to adverse effects. These data are vital to the understanding of plastic particulate toxicology and the developmental origins of health and disease.

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“…The results of our current study also corroborate data from previous nanotoxicological investigations from our group and others that have shown reduced fetal weight, or restricted fetal growth, after chronic maternal inhalation of nano-titanium dioxide particles [39,52]. We have previously postulated that diminished fetal development after maternal nanoparticle exposure is associated with indirect vascular de ciencies leading to uteroplacental ischemia in late-stages of pregnancy [39,53,54].…”

Section: Discussionsupporting

confidence: 91%

Nanopolystyrene translocation and fetal deposition after acute lung exposure during late-stage pregnancy

Fournier

¹

,

D’Errico

²

,

Adler

³

et al. 2020

Preprint

1

0

View full text Add to dashboard Cite

Background: Plastic is everywhere. It is used in food packaging, storage containers, electronics, furniture, clothing, and common single-use disposable items. Microplastic and nanoplastic particulates are formed from bulk fragmentation and disintegration of plastic pollution. Plastic particulates have recently been detected in indoor air and remote atmospheric fallout. Due to their small size, microplastic and nanoplastic particulate in the atmosphere can be inhaled and may pose a risk for human health, specifically in susceptible populations. When inhaled, nanosized particles have been shown to translocate across pulmonary cell barriers to secondary organs, including the placenta. However, the potential for maternal-to-fetal translocation of nanosized-plastic particles and the impact of nanoplastic deposition or accumulation on fetal health remain unknown. In this study we investigated whether nanopolystyrene particles can cross the placental barrier and deposit in fetal tissues after maternal pulmonary exposure.Results: Pregnant Sprague Dawley rats were exposed to 20 nm rhodamine-labeled nanopolystyrene beads (2.64 x 1014 particles) via intratracheal instillation on gestational day (GD) 19. Twenty-four hours later on GD 20, maternal and fetal tissues were evaluated using fluorescent optical imaging. Fetal tissues were fixed for particle visualization with hyperspectral microscopy. Using isolated placental perfusion, a known concentration of nanopolystyrene was injected into the uterine artery. Maternal and fetal effluents were collected for 180 minutes and assessed for polystyrene particle concentration. Twenty-four hours after maternal exposure, fetal and placental weights were significantly lower (7% and 8%, respectively) compared with controls. Nanopolystyrene particles were detected in the maternal lung, heart, and spleen. Polystyrene nanoparticles were also observed in the placenta, fetal liver, lungs, heart, kidney, and brain suggesting maternal lung-to-fetal tissue nanoparticle translocation in late stage pregnancy.Conclusion: These studies confirm that maternal pulmonary exposure to nanopolystyrene results in the translocation of plastic particles to placental and fetal tissues and renders the fetoplacental unit vulnerable to adverse effects. These data are vital to the understanding of plastic particulate toxicology and the developmental origins of health and disease.

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“…For engineered NMs, studies in experimental animals indicate that maternal NM exposure during gestation interferes with maternal vascular reactivity and placental vascular development and function. Exposure to NMs has been associated with increased tone and contractility of the uterine vasculature [162][163][164][165][166]. In some studies, placentas from exposed pregnant rats were larger, while their offspring were smaller compared to the control group, indicative of effects downstream from the uterine vascular impairment [163,166].…”

Section: Nm Interference With Vascular Signaling and Utero-placental mentioning

confidence: 99%

“…The study was performed in non-pregnant females, but the mechanisms ought to be also investigated during pregnancy. In another study, inhalation of TiO 2 NPs during pregnancy was found to augment vasoconstriction of the uterine artery in response to Kisspeptin [166]. Kisspeptin is a potent vasoconstrictor and an essential reproductive hormone, which is secreted by the placenta during late pregnancy at 10,000-fold higher levels compared to the non-pregnant state (reviewed in [168]).…”

Section: Nm Interference With Vascular Signaling and Utero-placental mentioning

confidence: 99%

“…Kisspeptin is a potent vasoconstrictor and an essential reproductive hormone, which is secreted by the placenta during late pregnancy at 10,000-fold higher levels compared to the non-pregnant state (reviewed in [168]). It is, therefore, possible that TiO 2 NP exposure perturbed the endocrine vascular axis via a kisspeptin-dependent mechanism [166]. Finally, a recent study investigated blood perfusion in placentas from pregnant rats inhaling TiO 2 NPs.…”

Section: Nm Interference With Vascular Signaling and Utero-placental mentioning

confidence: 99%

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Recent insights on indirect mechanisms in developmental toxicity of nanomaterials

Dugershaw

¹

,

Aengenheister

²

,

Hansen

³

et al. 2020

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Background: Epidemiological and animal studies provide compelling indications that environmental and engineered nanomaterials (NMs) pose a risk for pregnancy, fetal development and offspring health later in life. Understanding the origin and mechanisms underlying NM-induced developmental toxicity will be a cornerstone in the protection of sensitive populations and the design of safe and sustainable nanotechnology applications. Main body: Direct toxicity originating from NMs crossing the placental barrier is frequently assumed to be the key pathway in developmental toxicity. However, placental transfer of particles is often highly limited, and evidence is growing that NMs can also indirectly interfere with fetal development. Here, we outline current knowledge on potential indirect mechanisms in developmental toxicity of NMs. Short conclusion: Until now, research on developmental toxicity has mainly focused on the biodistribution and placental translocation of NMs to the fetus to delineate underlying processes. Systematic research addressing NM impact on maternal and placental tissues as potential contributors to mechanistic pathways in developmental toxicity is only slowly gathering momentum. So far, maternal and placental oxidative stress and inflammation, activation of placental toll-like receptors (TLRs), impairment of placental growth and secretion of placental hormones, and vascular factors have been suggested to mediate indirect developmental toxicity of NMs. Therefore, NM effects on maternal and placental tissue function ought to be comprehensively evaluated in addition to placental transfer in the design of future studies of developmental toxicity and risk assessment of NM exposure during pregnancy.

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Maternal Engineered Nanomaterial Inhalation During Gestation Disrupts Vascular Kisspeptin Reactivity

Cited by 24 publications

References 39 publications

Nanopolystyrene translocation and fetal deposition after acute lung exposure during late-stage pregnancy

Nanopolystyrene translocation and fetal deposition after acute lung exposure during late-stage pregnancy

Nanopolystyrene translocation and fetal deposition after acute lung exposure during late-stage pregnancy

Recent insights on indirect mechanisms in developmental toxicity of nanomaterials

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