According to the International Union of Pure and Applied Chemistry (IUPAC),
ultrafine particles or nanoparticles (NPs) are particles of matter of any shape
with dimensions between 1 m (1 10 m) and 100 m
(1 10 m) [1]; being smaller than visible light wavelengths
(400–700 m), NPs cannot be observed with common optical microscope,
demanding the use of an environmental scanning electron microscope (ESEM),
possibly coupled to an energy dispersive X-ray (EDX) spectroscope for elemental
microanalysis [2]. By virtue of this, NPs dispersions in transparent media are in
turn transparent; moreover, they easily pass through common filters, and the
separation from liquids needs nanofiltration techniques [3]. NPs can be of both
natural and artificial origin: natural ones derive from many cosmological,
geological and meteorological processes, while artificial ones are man made by
means of combustion processes [3]. An ultra-specialized branch of nanotechnology
is precisely focused on the realization of NPs with specific properties, while
nanotoxicology studies the toxicity of these NPs on the living beings [4]. Of the
possible hazards, inhalation and ingestion appear to present the most concern,
because of the high NPs surface-to-volume ratio, which makes them highly
catalytic or reactive [3]. In addition, they can receive a coating from
phospholipid bilayers, pass through cell membranes, and to aggregate together
[5]; obviously, a fetus body is more sensitive to environmental disruptors than
an adult [6, 7, 8]. As of 2013 the USA Environmental Protection Agency was testing
the safety of the following NPs: carbon nanotubes (CNTs), iron oxide NPs (FeO
NPs), silver NPs (Ag NPs), copper NPs (Cu NPs), cerium dioxide NPs (CeONPs), and titanium dioxide NPs (TiO NPs) [9]. A study on mice by Qi and
colleagues has highlighted that CNTs overcome the fetal-placental barrier, mainly
accumulating in the liver, lungs and heart of the fetus [10]. A further murine
model by Fujitani et al. [11] has showed that CNTs possess
teratogenicity at least under experimental conditions. Nanoscale iron is
increasingly used into nutrient supplement since better-absorbed; however, high
doses of (+) FeO NPs administered in a late stage of organogenesis are resulted
more fetotoxic in mice than equivalent doses of (–) FeO NPs [12]. Ag NPs are
currently being exploited into food packaging and for their antibacterial,
antifungal and antiviral properties (Fig. 1). Once ingested or inhaled during
pregnancy, they reach the placenta, increasing the expression of
pregnancy-relevant inflammatory cytokines, and inducing immunological dysfunction
in pregnant mice [13]. Prenatal exposure to Ag NPs can compromise postnatal
development of neonatal rats, especially the pulmonary, reproductive, immune and
neuronal functions [14, 15, 16, 17, 18, 19, 20, 21, 22, 23]; moreover, they show toxicity on endometrial
receptivity in female mice [24]. ESEM investigations have showed that placental
transfer of Ag NPs causes indentation of nuclei, clumped chromatin, pyknotic
nuclei and focal necrosis; therefore, further studies of genotoxicity have been
recommended [25]. Vidmar and colleagues have proved Ag NPs translocation in an
ex vivo human placenta perfusion model [26], while Gatti et al.
[27] have found Ag NPs in the human fetal brain of an unexplained stillbirth
suggesting a possible pathogenetic role. Cu NPs are used as preservatives in
pressure treated lumber and in some paints or coatings. Oral exposure of pregnant
mice to Cu NPs causes liver disorders in fetuses [28, 29]; moreover, they show
evident germinal toxicity via extracellular signal-regulated kinases (ERK)
pathway in female mice [30]. Prenatal exposure to Cu NPs triggers severe lung
inflammation in dams and immunomodulatory aftermaths in offspring [31]. CeO
NPs are used in fuel additives, electronics and biomedical supplies; a lot of
CeO NPs applications imply their dispersion in the environment, with a
consequent increase of polluting hazard. Both human cytotrophoblasts and
syncytiotrophoblasts can internalize CeO NPs, which influence trophoblastic
metabolic activity in a dose and time dependency, induce caspase activation, a
lactate dehydrogenase release, and disturb secretion of pregnancy-relevant
hormones [32]. In a murine model, maternal exposure to CeO NPs during early
pregnancy gives rise to placental dysfunctions, among which low-quality
decidualization and abnormal recruitment of uterine natural killer cells [33].
TiO NPs are currently exploited in sunscreens, cosmetics, paints and
coatings; they also find application into removing contaminants from drinking
water. Recent research from the northern China, performed under TiO NPs
mining exposure, has put in correlation the maternal blood Ti concentration with
low birth weight (LBW) risk. A total of 45 females who gave birth to LBW babies
(cases) and 352 females with no LBW newborns (controls) have been compared;
interestingly, median total blood Ti concentration in the cases group was
significantly higher than in the controls group (134 vs 129 g/mL,
p-value = 0.039) [34]. A human maternofetal transfer of TiO NPs
during pregnancy have been previously demonstrated, as well as an increase in
placental vascular resistance and an impairment in umbilical vascular reactivity
due to TiO NPs [35, 36]. Maternal exposure to TiO NPs during the
periconception period has been also correlated with a higher risk of neural tube
defects in human offspring [37]. In mice, TiO NPs exposure in pregnancy
significantly affects the placental development, most likely by dysregulating
proliferation, vascularization and apoptosis [38, 39, 40]. In addition, TiO2 NPs
exposure alters mice ovary resulting in hypofertility [41, 42]. In conclusion, all
these preliminary data suggest to protect pregnant women from high exposures of
NPs, and stimulate new research inside this pioneering field in the interest of
the whole community.
Fig. 1.
Example of ESEM image with spherical Ag NPs from a human
cellular substrate as confirmed by the Ag peak in the corresponding EDX spectrum
[X axis: KeV; Y axis: counts 10].
Ethics approval and consent to participate
Not applicable.
Acknowledgment
Not applicable.
Funding
This research received no external funding.
Conflict of interest
The author declares no conflict of interest. LR is serving as one of the Editorial Board members of this journal.
We declare that LR had no involvement in the peer review of this article and has no access to information regarding its peer review.
Full responsibility for the editorial process for this article was delegated to RG.
