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Plasticenta: First evidence of microplastics in human placenta

Authors:
  • Ospedale San Giovanni Calibita - Fatebenefratelli - Isola Tiberina - Roma

Abstract and Figures

Microplastics are particles smaller than five millimeters deriving from the degradation of plastic objects present in the environment. Microplastics can move from the environment to living organisms, including mammals. In this study, six human placentas, collected from consenting women with physiological pregnancies, were analyzed by Raman Microspectroscopy to evaluate the presence of microplastics. In total, 12 microplastic fragments (ranging from 5 to 10 μm in size), with spheric or irregular shape were found in 4 placentas (5 in the fetal side, 4 in the maternal side and 3 in the chorioamniotic membranes); all microplastics particles were characterized in terms of morphology and chemical composition. All of them were pigmented; three were identified as stained polypropylene a thermoplastic polymer, while for the other nine it was possible to identify only the pigments, which were all used for man-made coatings, paints, adhesives, plasters, finger paints, polymers and cosmetics and personal care products.
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Environment International 146 (2021) 106274
Available online 2 December 2020
0160-4120/© 2020 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Plasticenta: First evidence of microplastics in human placenta
Antonio Ragusa
a
, Alessandro Svelato
a
,
*
, Criselda Santacroce
b
, Piera Catalano
b
,
Valentina Notarstefano
c
, Oliana Carnevali
c
, Fabrizio Papa
b
, Mauro Ciro Antonio Rongioletti
b
,
Federico Baiocco
a
, Simonetta Draghi
a
, Elisabetta DAmore
a
, Denise Rinaldo
d
, Maria Matta
e
,
Elisabetta Giorgini
c
a
Department of Obstetrics and Gynecology, San Giovanni Calibita Fatebenefratelli Hospital, Isola Tiberina, Via di Ponte Quattro Capi, 39, 00186 Rome, Italy
b
Department of Pathological Anatomy, San Giovanni Calibita Fatebenefratelli Hospital, Isola Tiberina, Via di Ponte Quattro Capi, 39, 00186 Roma, Italy
c
Department of Life and Environmental Sciences, Universit`
a Politecnica delle Marche, via Brecce Bianche, 60131 Ancona, Italy
d
Department of Obstetrics and Gynecology, ASST Bergamo Est, Bolognini Hospital, Seriate, Via Paderno, 21, 24068 Bergamo, Italy
e
Harvey Medical and Surgery Course, University of Pavia, Corso Strada Nuova 65, 27100 Pavia, Italy
ARTICLE INFO
Handling Editor: Adrian Covaci
Keywords:
Human placenta
Microplastics
Raman microspectroscopy
ABSTRACT
Microplastics are particles smaller than ve millimeters deriving from the degradation of plastic objects present
in the environment. Microplastics can move from the environment to living organisms, including mammals. In
this study, six human placentas, collected from consenting women with physiological pregnancies, were analyzed
by Raman Microspectroscopy to evaluate the presence of microplastics. In total, 12 microplastic fragments
(ranging from 5 to 10
μ
m in size), with spheric or irregular shape were found in 4 placentas (5 in the fetal side, 4
in the maternal side and 3 in the chorioamniotic membranes); all microplastics particles were characterized in
terms of morphology and chemical composition. All of them were pigmented; three were identied as stained
polypropylene a thermoplastic polymer, while for the other nine it was possible to identify only the pigments,
which were all used for man-made coatings, paints, adhesives, plasters, nger paints, polymers and cosmetics
and personal care products.
1. Introduction
In the last century, the global production of plastics has reached 320
million tons (Mt) per year, and over 40% is used as single-use packaging,
hence producing plastic waste. In Europe, plastic production reached the
58 millions of tons in 2014 (PlasticsEurope, 2016). The degradation that
plastics undergo when released into the environment is a serious issue.
Atmospheric agents, such as waves, abrasion, ultraviolet radiation and
photo-oxidation in combination with bacteria degrade plastic fragments
into micro and nanosized particles. Most of the seabed all over the world
and in the Mediterranean Sea in particular, is made of plastic, resulting
from the waste collected on the coasts and in the sea (de Souza Machado
et al., 2018). Microplastics (MPs) are dened as particles less than 5 mm
in size (Hartmann et al., 2019). MPs do not derive only from larger
pieces fragmentation but are also produced in these dimensions for
commercial uses. Furthermore, there are several reports of MPs in food
(Barboza et al., 2018), and in particular in seafood, sea salt (Karami
et al., 2017b; Kosuth et al., 2018), and in drinking water (Schymanski
et al., 2018). Microplastics have also been detected in the gastrointes-
tinal tract of marine animals (Deng et al., 2017; Reineke et al., 2013),
and also human intestine (Schwabl et al., 2019). Inside tissues, MPs are
considered as foreign bodies by the host organism and, as such, trigger
local immunoreactions. Furthermore, MPs can act as carriers for other
chemicals, such as environmental pollutants and plastic additives,
which may be released and are known for their harmful effects (EFSA
Panel on Contaminants in the Food Chain (CONTAM), 2016; Wright and
Kelly, 2017).
In this study, for the rst time, several microplastic fragments were
detected by Raman Microspectroscopy in human placenta samples
collected from six consenting patients with uneventful pregnancies.
Raman Microspectroscopy is a well-assessed vibrational technique,
widely and successfully applied in the biomedical eld, to characterize
both biological samples (Notarstefano et al., 2020, 2019), and to detect
the occurrence of microplastics and microparticles in general (K¨
appler
et al., 2016; Ribeiro-Claro et al., 2017). Placenta nely regulates foetal
to maternal environment and, indirectly, to the external one, acting as a
* Corresponding author.
E-mail address: alessandrosvelato@virgilio.it (A. Svelato).
Contents lists available at ScienceDirect
Environment International
journal homepage: www.elsevier.com/locate/envint
https://doi.org/10.1016/j.envint.2020.106274
Received 16 August 2020; Received in revised form 29 October 2020; Accepted 9 November 2020
Environment International 146 (2021) 106274
2
crucial interface via different complex mechanisms (PrabhuDas et al.,
2015). The potential presence of man-made MPs in this organ may harm
the delicate response of differentiation between self and non-self (Nancy
et al., 2012) with a series of related consequences on embryo develop-
ment that need to be dened.
2. Materials and methods
2.1. Experimental design
This was a pilot observational descriptive preclinical study, with a
prospective and unicentric open cohort. It was approved by the Ethical
Committee Lazio 1 (Protocol N. 352/CE Lazio 1; March 31th, 2020), and
it was carried out in full accordance with ethical principles, including
The Code of Ethics of the World Medical Association (Declaration of
Helsinki) for experiments involving humans. To participate to this study,
six selected consenting patients signed an informed consent, which
included donation of placentas.
To prevent plastic contamination, a plastic-free protocol was adop-
ted during the entire experiment. Obstetricians and midwives used
cotton gloves to assist women in labour. In the delivery room, only
cotton towels were used to cover patientsbeds; graduate bags to esti-
mate postpartum blood loss were not used during delivery, but they
were brought in the delivery room only after birth, when umbilical cord
was already clamped and cut with metal clippers, avoiding contact with
plastic material. Pathologists wore cotton gloves and used metal
scalpels.
The schematic illustration for the overall concept and experimental
procedure is reported in Fig. 1.
2.2. Enrolment of patients and placentas collection
All recruited women were healthy and have a vaginal delivery at
term of pregnancy at the Department of Obstetrics and Gynaecology of
San Giovanni Calibita Fatebenefratelli Hospital, Isola Tiberina, Roma
(Italy). They were selected according to the following exclusion criteria:
diagnosis of gastrointestinal disease, such as ulcerative colitis, or
Crohns disease, cancer, organ transplantation, HIV (Human Immuno-
deciency Virus), or other severe pathologies; alcohol abuse (dened as
a >10 score in the Alcohol Use Disorders Identication Test); cigarette
smoking; peculiar diets prescribed for particular medical conditions
(four weeks before delivery); diarrhoea or constipation (two weeks
before delivery); antibiotics intake (two weeks before delivery);
assumption of drugs affecting intestinal reabsorption, such as activated
charcoal, or cholestyramine (two weeks before delivery); invasive or
abrasive dental treatments (two weeks before delivery); participation to
Fig. 1. Schematic illustration for the overall concept and experimental procedure followed in the study.
A. Ragusa et al.
Environment International 146 (2021) 106274
3
a clinical study (four weeks before delivery). Women were also asked to
ll a questionnaire to record their food consumption (omnivorous,
vegetarian, vegan, with no diet restriction) the week before delivery and
the use of toothpastes and cosmetics containing MPs or synthetic
polymers.
After birth, placentas were deposed onto a metal container and
immediately sectioned in portions (mean weight: 23.3 ±5.7 g) taken
from maternal side, foetal side, and chorioamniotic membranes. All
samples were strictly anonymous; they were labelled with number codes
and stored in glass bottles with metal lids at 20 C with no further
treatment.
2.3. Digestion of placenta samples
The digestion of placenta samples was performed at the Laboratory
of Vibrational Spectroscopy, Department of Life and Environmental
Sciences, Universit`
a Politecnica delle Marche (Ancona, Italy), modifying
as follows the protocols from two previous works (Dehaut et al., 2016;
Karami et al., 2017a). Samples were weighed and placed in a glass
container. A 10% KOH solution was prepared using 1.6 µm-ltered
deionised water and KOH tablets (Sigma-Aldrich). This solution was
added to each jar in a ratio with the sample of 1:8 (w/v). The containers
were then sealed and incubated at room temperature for 7 days. To
prevent plastic contamination, cotton laboratory coats, face masks and
single-use latex gloves were worn during sample handling, preparation
of samples and during the entire experiment. Work surfaces were thor-
oughly washed with 70% ethanol prior starting all procedures. All liq-
uids (deionised water for cleaning and for preparation of KOH solution)
were ltered through 1.6 µm-pore-size lter membrane (Whatman GF/
A). Glassware and instruments, including scissors, tweezers and scalpels,
were washed using dishwashing liquid, rinsed with deionised water and
nally rinsed with 1.6 µm-ltered deionised water. Since the experi-
ments were conducted without the use of the laminar ow hood, the
plastic bres found in the samples were not considered in the results.
Digestates were then ltered through 1.6 µm-pore-size lter membrane
(Whatman GF/A) using a vacuum pump connected to a lter funnel. The
lter papers were dried at room temperature and stored in glass Petri
dishes until visual identication and spectroscopic characterization of
plastic particles. Three procedural blanks, obtained following the same
procedure above described, but without placenta samples and main-
tained close to the samples during their manipulation, were tested to
monitor and correct potential contaminations (Karami et al., 2017a).
2.4. Analysis of microplastics by Raman Microspectroscopy
The Raman analysis of MPs was performed at the Laboratory of
Vibrational Spectroscopy, Department of Life and Environmental Sci-
ences, Universit`
a Politecnica delle Marche (Ancona, Italy). Filter mem-
branes were rst inspected by visible light using a ×10 objective
(Olympus MPLAN10x/0.25). The detected MPs were morphologically
characterized by a ×100 objective (Olympus MPLAN100x/0.90), and
then directly analyzed on the lter by Raman Microspectroscopy
(spectral range 1602000 cm
1
, 785 nm laser diode, 600 lines per mm
grating). A Raman XploRA Nano Microspectrometer (Horiba Scientic)
was used. The spectra were dispersed onto a 16-bit dynamic range
Peltier cooled CCD detector; the spectrometer was calibrated to the
520.7 cm
1
line of silicon prior to spectral acquisition. Raw Raman
spectra were submitted to polynomial baseline correction and vector
normalization, in order to reduce noise and enhance spectrum quality
(Labspec 6 software, Horiba Scientic). The collected Raman spectra
were compared with those reported in the SLOPP Library of Micro-
plastics (SLOPP Library of Microplastics,n.d.) and in the spectral li-
brary of the KnowItAll software (Bio-Rad Laboratories, Inc.). Similarities
of more than 80 of Hit Quality Index (HQI) were considered satisfactory.
3. Results
From each placenta, three portions with a mean weight of 23.3 ±5.7
g were collected from the maternal side, the foetal side and the cho-
rioamniotic membranes. All portions were opportunely processed for
the subsequent analysis by Raman Microspectroscopy.
In total, 12 MP fragments (named #1#12) were detected in the
placentas of four women; more in detail, 5 MPs were found in the foetal
side portions, 4 in the maternal side portions, and 3 in the cho-
rioamniotic membranes. Microplastics #1#4, #6, #7, and #9#12,
were ~10
μ
m in size, while #5 and #8 ones were smaller (~5
μ
m). All
the analyzed MPs were pigmented.
A retrospective analysis based on Raman spectral information and
data reported in literature was performed to dene the nature of these
MPs. Firstly, the collected Raman spectra were compared with those
stored in the spectral library of the KnowItAll software (Bio-Rad Labo-
ratories, Inc.). In many cases, the collected Raman spectra showed,
above all, the contribution of the pigments used for plastic staining
(Imhof et al., 2016; Stoye and Freitag, 1998); it is known that the con-
jugated rings present in pigment molecules are highly polarizable and,
hence, their Raman signals are more intense than those of the apolar
polymeric matrix (K¨
appler et al., 2016). In these cases, the KnowItAll
software identied the pigments contained in the MPs. By matching the
results from the KnowItAll software with the information obtained by
consulting the European Chemical Agency, ECHA (European Chemical
Agency,n.d.), it was possible to accurately identify the commercial
name, chemical formula, IUPAC name and Color Index Constitution
Number of all pigments. Further, in order to uncover the identity of the
polymer matrix of the detected MPs, the collected Raman spectra were
also compared with those reported in the SLOPP library of Microplastics.
The identied MPs were differentiated between stained MPs (parti-
cles #2, #10 and #11, identied as polypropylene) and paint/coating/
dye MPs (particles #1, #39, and #12), which are applied for paints,
coatings, adhesives, plasters, polymers and cosmetics and personal care
products (Imhof et al., 2016).
The microphotographs and the Raman spectra of all analysed MPs
are shown in Fig. 2, while Table 1 reports their morphological and
chemical characterization. The spectral analysis is reported below.
Particle #1 (Fig. 2a): the Raman spectrum resulted superimposable
to the one of the pigment Iron hydroxide oxide yellow (main peak at 396
cm
1
, related to the vibrations of iron oxides/hydroxides) (Sklute et al.,
2018).
Particles #2, #5, and #10 (Fig. 2b, e): the Raman spectra resulted
comparable to the one of a polypropylene (PP) blue sample, sharing the
main peaks at 253 cm
1
(wagging of CH
2
moieties, bending of CH
moieties), 397 cm
1
(wagging of CH
2
moieties, bending of CH moieties),
839 cm
1
(rocking of CH
2
and CH
3
moieties, stretching of CC and C-CH
3
moieties), 970 cm
1
(rocking of CH
3
moieties), and 1455 cm
1
(bending
of CH
3
and CH
2
moieties), all assigned to PP (Andreassen, 1999). The
bands at 679 cm
1
, 1143 cm
1
, 1340 cm
1
and 1527 cm
1
, common to
reference blue polypropylene and sample spectra, are known to be
related to Raman signals of blue pigments, mainly based on copper
phthalocyanine (Aguayo et al., 2010; Scherrer et al., 2009).
Particle #3 (Fig. 2c): the Raman spectrum resulted superimposable
to the one of the blue pigment phthalocyanine, sharing the main peaks at
679 cm
1
, 1143 cm
1
, 1340 cm
1
and 1527 cm
1
(Aguayo et al., 2010;
Scherrer et al., 2009).
Particle #4 (Fig. 2d): the Raman spectrum resulted superimposable
to the one of the pigment violanthrone, with the two main peaks
centered at 1577 cm
1
(C-C stretching of benzene ring) and 1307 cm
1
(in reference spectrum, an additional shoulder at ~1350 cm
1
is visible,
assigned to C-C stretching and HC-C bending) (Socrates, 2001).
Particles #6 and #7 (Fig. 2f): the Raman spectra resulted super-
imposable to the one of the red pigment oxo(oxoferriooxy)iron (main
peaks at 220, 287 and 401 cm
1
, typical of iron oxides) (Testa-Anta
et al., 2019).
A. Ragusa et al.
Environment International 146 (2021) 106274
4
Particle #8 (Fig. 2g): the Raman spectrum resulted superimposable
to the one of the pigment Direct Blue 80, showing two main peaks at 578
cm
1
and 1275 cm
1
(both assigned to ring deformations of substituted
benzene) (Socrates, 2001).
Particle #9 (Fig. 2h): the Raman spectrum resulted superimposable
to the one of the pigment Ultramarine Blue, with one main peak centred
at 525 cm
1
, assigne to orthosilicate vibration modes (Socrates, 2001).
Particle #11 (Fig. 2i): the Raman spectrum resulted comparable to
the one of a PP purple ber, sharing the main peaks of PP (Andreassen,
1999) (397 cm
1
, assigned to the wagging of CH
2
moieties/bending of
Fig. 2. Microphotographs and Raman spectra of the microplastics found in human placenta: (a) Particle #1 (scale bar 5
μ
m); (b) Particles #2 and #10 (scale bar 5
μ
m
for #2 and 10
μ
m for #10); (c) Particle #3 (scale bar 5
μ
m); (d) Particle #4 (scale bar 5
μ
m); (e) Particle #5 (scale bar 5
μ
m); (f) Particles #6 and #7 (scale bar 10
μ
m
for #6 and 5
μ
m for #7); (g) Particle #8 (scale bar 10
μ
m); (h) Particle #9 (scale bar 10
μ
m); (i) Particle #11 (scale bar 5
μ
m), and (l) Particle #12 (scale bar 10
μ
m).
A. Ragusa et al.
Environment International 146 (2021) 106274
5
CH moieties, and 1455 cm
1
, assigned to the bending of CH
3
and CH
2
moieties), and also of the violet pigment (1193 cm
1
, 1335 cm
1
and
1381 cm
1
) (Scherrer et al., 2009).
Particle #12 (Fig. 2j): the collected Raman spectrum resulted su-
perimposable to the one of the pink pigment Novoperm Bordeaux HF3R.
The Raman spectrum of this monoazopigment shared with the sample
spectrum the main peaks centered at 731 cm
1
, 961 cm
1
, 1219 cm
1
,
1280 cm
1
, 1360 cm
1
, and 1580 cm
1
. This pigment is reported to be
used to permanently coat and protect wood surfaces, in photographic
chemicals, inks and toners, given its high solvent resistance and good
heat stability (Scherrer et al., 2009).
4. Discussion
This is the rst study revealing the presence of pigmented micro-
plastics and, in general, of man-made particles in human placenta. The
presence of pigments in all analysed MPs is explained by the wide use of
these compounds to colour not only plastic products, but also paints and
coatings, which are as ubiquitous as MPs (Imhof et al., 2016). For
example, the pigment Iron hydroxide oxide yellow (particle #1) is used
for coloration of polymers (plastics and rubber) and in a wide variety of
cosmetics, such as BB creams and foundations; copper phthalocyanine
(particles #2, #5, #10,) and phthalocyanine (particle #3) are used for
staining of plastic materials (polyvinylchloride, low density poly-
ethylene, high density polyethylene, polypropylene, polyethylene tere-
phthalate), and for nger paints; the pigment violanthrone (particle #4)
is used especially for textile (cotton/polyester) dyeing, coating products,
adhesives, fragrances and air fresheners; the pigment Ultramarine blue
is mainly applied in cosmetics, for example for formulations of soap,
lipstick, mascara, eye shadow and other make-up products.
For the rst time, by means of Raman Microspectroscopy, 12 MP
fragments were isolated in four human placentas. In particular, 5 MPs
were found in the foetal side, 4 in the maternal side and 3 in the cho-
rioamniotic membranes, indicating that these MPs, once inside the
human body, can reach placenta tissues at all levels. It is noteworthy to
remark that small portions of placentas (~23 g with respect to a total
weight of ~600 g) were analysed, letting hypothesize that the number of
MPs within the entire placenta is much higher.
The dimensions of all MPs were ~10
μ
m in size, except for two that
were smaller (~5
μ
m). These values are compatible with a possible
transportation by bloodstream. In fact, previous analyses performed by
means of Electron Microscopy coupled with an X-ray microprobe,
revealed the presence of 510
μ
m particles as foreign bodies in human
internal organs (Vaseashta, 2015).
Unfortunately, we do not know how MPs reach the bloodstream and
if they come from the respiratory system or the gastrointestinal system.
Fig. 3 shows the possible ways of entry and transport of the MPs from the
respiratory and gastric organs to the placenta.
The presence of MPs in the placenta tissue requires the reconsider-
ation of the immunological mechanism of self-tolerance. Placenta rep-
resents the interface between the foetus and the environment
(PrabhuDas et al., 2015). Embryos and foetuses must continuously adapt
to the maternal environment and, indirectly, to the external one, by a
series of complex responses. An important part of this series of responses
consists in the ability to differentiate self and non-self (Nancy et al.,
2012), a mechanism that may be perturbed by the presence of MPs. In
fact, it is reported that, once present in the human body, MPs may
accumulate and exert localized toxicity by inducing and/or enhancing
immune responses and, hence, potentially reducing the defence mech-
anisms against pathogens and altering the utilization of energy stores
(Wright and Kelly, 2017).
Microplastics may access the bloodstream and reach placenta from
the maternal respiratory system (Schlesinger, 1988) and the gastroin-
testinal tract (GIT) (Arumugasaamy et al., 2019), by means of M cells-
Table 1
Size, color and chemical features of the detected microplastics and relative pigments, together with information regarding the placenta portion in which they were
found (fetal side FS; maternal side MS, and chorioamnio membrane CAM; not dened n.d.; Hit Quality Index HQI).
Particle Placenta
Portion
Microparticles
Size Color Polymer
matrix
Pigment
Generic name Molecular formula and IUPAC name HQI
#1 FS ~10
μ
m
Orange n.d. Iron hydroxide oxide yellow
(Pigment Yellow 43; C.I.
Constitution 77492)
FeO(OH)
iron(III) oxide hydroxide
89.97
#2 CAM ~10
μ
m
Blue Polypropylene Copper phthalocyanine (Pigment
Blue 15; C.I. Constitution 74160)
C
32
H
16
CuN
8
(29H,31H-phthalocyaninato(2 )-N29,N30,N31,N32)copper(II)
82.86
#3 FS ~10
μ
m
Blue n.d. Phthalocyanine Blue BN (Pigment
Blue 16; C.I. Constitution 74100)
C
32
H
18
N
8
29H,31H-phthalocyanine 89.16
#4 MS ~10
μ
m
Dark
blue
n.d. Violanthrone (Pigment Blue 65; C.
I. Constitution 59800)
C
34
H
16
O
2
Anthra[9,1,2-cde]benzo[rst]pentaphene-5,10-dione 86.44
#5 MS ~5
μ
m
Blue Polypropylene Copper phthalocyanine (Pigment
Blue 15; C.I. Constitution 74160)
C
32
H
16
CuN
8
(29H,31H-phthalocyaninato(2)-N29,N30,N31,
N32)copper(II)
86.15
#6 MS ~10
μ
m
Red n.d. Diiron trioxide (Pigment Red
101/102; C.I. Constitution 77491)
Fe
2
O
3
Oxo(oxoferriooxy)iron
83.65
#7 MS ~10
μ
m
Red n.d. Diiron trioxide (Pigment Red
101/102; C.I. Constitution 77491)
Fe
2
O
3
Oxo(oxoferriooxy)iron 89.80
#8 CAM ~5
μ
m
Dark
blue
n.d. Pigment Direct Blue 80 C
32
H
14
Cu
2
N
4
Na
4
O
16
S
4
Dicopper,tetrasodium,3-oxido-4-[[2-oxido-4-[3-oxido-4-[(2-
oxido-3,6-disulfonatonaphthalen-1-yl)diazenyl] phenyl]phenyl]
diazenyl]naphthalene-2,7-disulfonate
84.55
#9 CAM ~10
μ
m
Dark
blue
n.d. Ultramarine Blue (Pigment Blue
29; C.I. Constitution 77007)
Al
6
Na
8
O
24
S
3
Si
6
Aluminium Sodium orthosilicate trisulfane-1,3-diide
91.96
#10 FS ~10
μ
m
Blue Polypropylene Copper phthalocyanine (Pigment
Blue 15; C.I. Constitution 74160)
C
32
H
16
CuN
8
(29H,31H-phthalocyaninato(2)-N29,N30,N31,
N32)copper(II)
80.60
#11 FS ~10
μ
m
Violet Polypropylene Hostopen violet (Pigment Violet
23; C.I. Constitution 51319)
C
34
H
22
Cl
2
N
4
O
2
8,18-Dichloro-5,15-diethyl-5,15-dihydrodiindolo(3,2-b:3,2-m)
tri- phenodioxazine
80.92
#12 FS ~10
μ
m
Pink n.d. Novoperm Bordeaux HF3R
(Pigment Violet 32; C.I.
Constitution 12517)
C
27
H
24
N
6
O
7
S
4-[(E)-2-[2,5-dimethoxy-4-(methylsulfamoyl)phenyl]diazen-1-
yl]-3-hydroxy-N-(2-oxo-2,3-dihydro-1H-1,3-benzodiazol-5-yl)
naphthalene-2-carboxamide
84.57
A. Ragusa et al.
Environment International 146 (2021) 106274
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(caption on next page)
A. Ragusa et al.
Environment International 146 (2021) 106274
7
mediated endocytosis mechanisms or paracellular transport. The most
probable transport route for MPs is a mechanism of particle uptake and
translocation, already described for the internalization from the GIT
(Smith et al., 2018). The subsequent translocation to secondary target
organs, usually associated with inammatory responses in the sur-
rounding tissues, such as the immune activation of macrophages and the
production of cytokines (Hicks et al., 1996), depends on several factors,
including hydrophobicity, surface charge, surface functionalization and
the associated protein corona, and particle size.
Once MPs have reached the maternal surface of the placenta, as other
exogenous materials, they can invade the tissue in depth by several
transport mechanisms, both active and passive, that are not clearly
understood yet (Tetro et al., 2018). The transplacental passage of 510
μ
m size MPs may depend on different physiological conditions and ge-
netic characteristics. This might explain, together with the diverse food
habits and lifestyle of patients, the absence of MPs in 2 of the 6 analyzed
placentas and the different localization and characteristics of the parti-
cles identied in the present study. It is known that a great variability
exists in the expression and function of placental drug transporters, both
within human populations (inter-individual variability) and also during
gestation (intra-individual variability) (Staud and Ceckova, 2015). We
suppose that this variability exists also in relation to the mechanism of
particlesinternalization.
Potentially, MPs, and in general microparticles, may alter several
cellular regulating pathways in placenta, such as immunity mechanisms
during pregnancy, growth-factor signalling during and after implanta-
tion, functions of atypical chemokine receptors governing maternal-
foetal communication, signalling between the embryo and the uterus,
and trafcking of uterine dendritic cells, natural killer cells, T cells and
macrophages during normal pregnancy. All these effects may lead to
adverse pregnancy outcomes including preeclampsia and fetal growth
restriction (Ilekis et al., 2016).
In conclusion, this study sheds new light on the level of human
exposure to MPs and microparticles in general. Due to the crucial role of
placenta in supporting the foetus development and in acting as an
interface between the latter and the external environment, the presence
of exogenous and potentially harmful (plastic) particles is a matter of
great concern. Possible consequences on pregnancy outcomes and foetus
are the transgenerational effects of plasticizer on metabolism and
reproduction (Lee, 2018). Further studies need to be performed to assess
if the presence of MPs in human placenta may trigger immune responses
or may lead to the release of toxic contaminants, resulting harmful for
pregnancy.
Declaration of Competing Interest
The authors declare that they have no known competing nancial
interests or personal relationships that could have appeared to inuence
the work reported in this paper.
Acknowledgements
We thank all San Giovanni Calibita Fatebenefratelli Hospital staff for
their collaboration during the study and placentas collection, and the
Department of Life and Environmental Sciences, Universit`
a Politecnica
delle Marche for making available the instrumentation. We also thank
MIUR for nancial support (Ricerca Scientica di Ateneo 2018/19, Prof.
Elisabetta Giorgini).
The authors thank the Holy Father Francis for the inspiration they
drew from reading his encyclical Laudato si on care for our common
home’”
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Epithelial barriers are the body’s natural defense system to regulating passage from one domain to another. In our efforts to understand what can and cannot cross these barriers, models have emerged as a reductionist approach to rigorously study and investigate this question. In particular, in vitro tissue models have become prominent as there is an increased exploration of understanding biological molecular transport. Herein, we introduce the pertinent physiology, then discuss recent studies and approaches for building models of five epithelial tissues: skin, the gastrointestinal tract, the lungs, the blood–brain barrier, and the placenta. In particular, we evaluated literature from the past 5 years utilizing a tissue model to evaluate molecular transport. We then compare physiology of these tissues and discuss similarities in approaches, across tissues, to validate these models. We conclude with a summary of the approaches of growing interest across multiple tissues and an outlook on future steps to improve these models.