Recent insights on indirect mechanisms in developmental toxicity of nanomaterials

Abstract

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.

Teratogenic Effect of High Dose of Syzygium guineense (Myrtaceae) Leaves on Wistar Albino Rat Embryos and Fetuses

“…When the toxic agents cross the placental membrane, they directly damage the developing embryonic/fetal tissue. Indirectly, toxicants that damage the placental tissue and compromise placental function might impede the development of embryos/fetuses [ 38 , 39 ]. There has been no published study conducted on the teratogenicity of S. guineense .…”

Fetotoxicity of Nanoparticles: Causes and Mechanisms

“…In an early study, it was hypothesized that diffusion, transtrophoblastic channels, and/or receptor-mediated endocytosis were the potential mechanisms involved in the translocation of AuNPs (1.4- and 18-nm) [ 121 ]. In addition, the physicochemical characteristics of NPs, including chemical composition, hydrophilicity, and surface charge, might influence the transport of NPs to the fetus through interacting with the receptors of trophoblast cells [ 38 ].…”

“…Maternal NP exposure may induce fetotoxicity by the direct translocation of NPs to the fetus or indirect NP-induced maternal and placental mediators [ 37 , 38 , 117 ]. During the critical window of fetal development, the factors interfering with the whole process of gestation (maternal condition, placental function, and developing fetus), contribute to detrimental fetal outcomes.…”

“…So far, numerous studies have indisputably demonstrated that maternal exposure to nanomaterials during gestation result in fetotoxicity, including adverse prenatal effects on the fetus [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ], neurotoxicity [ 18 , 19 , 20 , 21 , 22 , 23 ], reproductive toxicity [ 24 , 25 , 26 , 27 , 28 ], immunotoxicity [ 29 , 30 , 31 , 32 ] and respiratory toxicity [ 29 , 33 , 34 , 35 ] in offspring or even in adulthood [ 16 , 17 , 18 , 36 ]. The direct translocation of NPs or indirect interference from maternal damage-induced maternal mediators and placental mediators contributes to the fetotoxicity induced by prenatal exposure to NPs [ 37 , 38 ].…”

Transition Metals Doped Nanocrystals: Synthesis, Characterization, and Applications

“…The ZnO NPs wide spectrum of applications makes it susceptible to entering the environment through various paths, such as effluents, spillage during transport, handling, direct contact through topical and oral consumer products, and incorrect disposal [8]. Such factors lead to contamination of environments and consequently adverse effects for humans and animals, such as excessive induction of reactive species, which can cause oxidative stress and trigger a cascade of damage in macromolecules, genotoxicity, apoptosis, neurotoxicity, and negative implications for embryonic development [9,10]. We have shown that amorphous zinc oxide nanoparticles have greater genotoxicity than crystalline (nanocrystals -NCs) [11].…”