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3.7 5.

Review

The Plastic Within: Microplastics


Invading Human Organs and Bodily
Fluids Systems

Christian Ebere Enyoh, Arti Devi, Hirofumi Kadono, Qingyue Wang and Mominul Haque Rabin

Special Issue
Plastic Contamination: Challenges and Solutions Volume II
Edited by
Dr. Teresa A. P. Rocha-Santos and Dr. Ana Luísa Patrício da Silva

https://doi.org/10.3390/environments10110194
environments

Review
The Plastic Within: Microplastics Invading Human Organs and
Bodily Fluids Systems
Christian Ebere Enyoh 1, * , Arti Devi 1 , Hirofumi Kadono 1 , Qingyue Wang 1 and Mominul Haque Rabin 1,2

1 Graduate School of Science and Engineering, Saitama University, 255 Shimo-Okubo, Sakura-ku,
Saitama City 338-8570, Japan; devi.a.542@ms.saitama-u.ac.jp (A.D.); kadono@mail.saitama-u.ac.jp (H.K.);
seiyo@mail.saitama-u.ac.jp (Q.W.); rabinagch@sau.edu.bd (M.H.R.)
2 Department of Agricultural Chemistry, Faculty of Agriculture, Sher-e-Bangla Agricultural University,
Dhaka 1207, Bangladesh
* Correspondence: cenyoh@gmail.com

Abstract: Microplastics (MPs), small plastic particles resulting from the degradation of larger plastic
items and from primary sources such as textiles, engineered plastic pellets, etc., have become a
ubiquitous environmental pollutant. As their prevalence in the natural environment grows, concerns
about their potential impacts on human health have escalated. This review discusses current research
findings on the presence of MPs in organs such as the liver, blood, heart, placenta, breast milk, sputum,
semen, testis, and urine, while also exploring plausible mechanisms of translocation. Furthermore,
the review emphasizes the importance of understanding the potential toxicological effects of MPs
on various physiological processes within these organs and their broader implications for human
health. This review also examines the pathways through which MPs can enter and accumulate in
human organs and bodily fluids, shedding light on the intricate routes of exposure and potential
health implications. It is worth noting that the invasive medical procedures may permit direct access
of MPs to the bloodstream and tissues, serving as a potential contamination source. However, it is
evident that a comprehensive understanding of MPs’ invasion into human organs is vital for effective
mitigation strategies and the preservation of both human health and the environment.

Citation: Enyoh, C.E.; Devi, A.;


Keywords: circulatory system; exposure pathways; health implications; human body; translocation
Kadono, H.; Wang, Q.; Rabin, M.H.
mechanisms; environmental contaminants; plastic particles; toxicological effects
The Plastic Within: Microplastics
Invading Human Organs and Bodily
Fluids Systems. Environments 2023,
10, 194. https://doi.org/10.3390/
environments10110194 1. Introduction
Production of plastics has significantly increased since they were originally developed
Academic Editors: Teresa A. P.
in the 1950s [1]. The environment’s plastics, which frequently come from improperly
Rocha-Santos and Ana Luísa Patrício
da Silva
disposed of consumer goods, slowly deteriorate due to photo and thermooxidative pro-
cesses and, to a lesser extent by biodegradation. As a result, the material becomes less
Received: 16 August 2023 stable and breaks down into secondary MPs, which are fragments smaller than 5 mm [2].
Revised: 30 October 2023 According to Browne et al. [3], primary MPs are defined as plastic particles of this size that
Accepted: 1 November 2023 are intentionally produced for use in products (such as toothpaste or cosmetic exfoliants)
Published: 10 November 2023
or by companies (such as air blasting). MPs pollution has been noted as a rising worldwide
problem over the past ten years that may have an impact on ecosystems, biodiversity, and
human health [4]. They are persistent pollutants that have been identified as a developing
Copyright: © 2023 by the authors.
global problem [5].
Licensee MDPI, Basel, Switzerland. MPs have been found in a wide range of environments, including freshwater [6–8],
This article is an open access article seawater [9,10], sediment [11,12], soil [13,14], street dust [15], air [16,17], and even consum-
distributed under the terms and ables such as beer, sea salt, and tap water [18]. Due to the significant deposits of MPs, the
conditions of the Creative Commons modern era has been referred to as “a new historical epoch, the Plasticene” [19]. Recent
Attribution (CC BY) license (https:// research has shown that MPs regularly enter the human body through ingestion, inhalation,
creativecommons.org/licenses/by/ and dermally, posing a serious threat to health [20]. According to Galloway [21], ingestion
4.0/). is the major route for entering MPs in the human body. The predicted intake of MPs is

Environments 2023, 10, 194. https://doi.org/10.3390/environments10110194 https://www.mdpi.com/journal/environments


Environments 2023, 10, 194 2 of 18

39,000–52,000 particles per person per year based on food consumption [22]. Particles
may enter the digestive tract through contaminated food or through mucociliary clearance
following inhalation, which may trigger an inflammatory response, increase permeability,
and alter the composition and metabolism of the gut microbes [23]. According to Prata [24],
each person inhales 26–130 airborne MPs every day. A male person with light exercise is
predicted to inhale 272 MPs each day based on air sampling using a mannequin [25,26]. The
size and density of the particles will affect how they deposit on the respiratory system, with
less dense and smaller particles penetrating the lungs deeper. Particle translocation may
occur after deposition as a result of macrophage clearance, migration to the bloodstream,
or lymphatic system. Dermal contact with MPs is considered a less significant route of
exposure, although it has been speculated that nanoplastics (NPs <100 nm) could transverse
the dermal barrier [27]. Human epithelial cells suffer oxidative stress from exposure to
MPs and NPs as well [28]. Although research on the interactions between MPs and other
human organs is ongoing, human absorption models of nanomaterials created by diverse
industrial production methods can be used to estimate the potential impacts of MPs. They
have been demonstrated to infiltrate the food chain [4], and as a result, they have also
been found in human stools [29] and human blood of healthy donors [30]. Due to the
prevalence of stool contamination after vaginal birth and investigated that human placenta
from caesarean deliveries contains MPs (>50 µm).
From these pathways, MPs have recently been reported in unimaginable parts of the
body and bodily fluid systems such as liver [31], blood [31,32], heart [32], placenta [33],
breast milk [34], sputum [35], semen [36], testis [36], and urine [37]. This review shines a
spotlight on the lesser-known and more unsettling aspect of plastic pollution: the infiltration
of MPs into the human body. Through various mechanisms, such as ingestion, inhalation,
and dermal absorption, these tiny plastic particles have managed to enter our bloodstream,
lymphatic system, and organs. The implications of this phenomenon for human health are
profound and multifaceted, as MPs may carry toxic additives, adsorb harmful chemicals,
and trigger inflammatory responses. The review examines the pathways through which
MPs enter the body, exploring the role of contaminated air, water, and food sources. It
also investigates the extent to which MPs are capable of translocating within the body,
potentially leading to accumulation in critical organs such as the liver, kidneys, and even
the heart. Researchers are actively working to understand the long-term consequences
of such internal plastic exposure, including the possible links to chronic diseases such as
cancer, autoimmune disorders, and neurological conditions [31–37].
The review then takes a critical turn, examining the growing body of research suggest-
ing potential health implications linked to MPs exposure. Although the full scope of these
health effects is not yet fully understood, the review highlights some concerning findings,
such as the ability of MPs to inhibit active enzymes and the potential for inflammation and
oxidative stress caused by their presence in bodily tissues. It also underscores the need for
further studies to elucidate the long-term consequences of this silent invasion.

2. MPs in the Human Body and Bodily Fluids System


Recent studies are now discovering MPs in more different human organ and bodily
systems such as the liver, blood, heart, placenta, breast milk, sputum, semen, testis and
urine. These studies are summarized in Table 1, presenting the extraction and analytical
methods, particle types, shapes and quantities found. Most studies have relied on potas-
sium hydroxide (KOH) for sample digestions while Proteinase K and calcium chloride
(CaCl2 ) was applied in one study [30]. The highest number of particles were reported in
the sputum and the least were reported in the semen.
Environments 2023, 10, 194 3 of 18

Table 1. Summary of MPs studies in different human organ and bodily systems.

Organ/ Analytical
Extraction Method Particle Types Shapes Quantity Reference
Fliuds Method Used
PS, PVC, PET,
KOH + NaHOCl (2:1), Fragments and 4.6 MPs/g (median)
Liver µRaman PMMA, POM, [31]
H2 O2 and ethanol microbeads ranging 4~30 µm
and PP
PET (2.4 µg/mL), PS
(4.8 µg/mL), PE
Proteinase K and PET, PS, PE,
Py-GC/MS - (7.1 µg/mL), PMMA [30] +
CaCl2 PMMA and PP
(0.36 µg/mL) and PP
Blood (0.94 µg/mL)
PET, PU, PS, PA,
30 wt % H2 O2 and PA (49%) and PET
LD-IR and SEM PVC, PE, PP, PC, Threads and rods [32] ++
ethanol (22%).
PMMA
30 wt % H2 O2 ,
PET, PU, PS, PA,
68 wt % HNO3 and PET (77%) and PU
Heart LD-IR and SEM PVC, PE, PP, PC, Threads and rods [32] ++
10 wt % NaOH, and (12%)
PMMA
ethanol
PP with some
spherical or 12 MP particles,
10% KOH µRaman other non-identify [33]
irregular shape ranging 5 to10 µm.
fragments
11 polymer types
were identified
Placenta 2.70 ± 2.65 particles/g
including PSF.
spherical or (0.28 to 9.55 particles/g).
10% KOH LD-IR Mainly PVC [38]
irregular shape Size ranged from
(43.27%), PP
20.34 to 307.29 µm
(14.55%), PBS
(10.90%)
PP, PVC, PE, PS, Sphere/ 48 MPs fragments
Breast Milk 10% KOH µRaman [34]
PES, and PEMA Irregular 2~12 µm.
Sample + 70% ethanol
21 types of MPs
(1:4) then with HNO3
PU, PES, alkyd narrower and 18.75~91.75 parti-
Sputum (68%) and NaOH µFTIR [35]
varnish longer cles/10 mL,
(neutralization) then
Size > 500 µm in siz
with ZnCl2
Fibers, fragments, 24 MPs size ranging
LD-IR and PVC, PE, PA, PS,
Semen KOH films, and 21.76~286.71 µm [36]
Py-GC/MS PP and PET
subspherical 0~2.06 particles/mL
4 MPs size ranging from
LD-IR and PS, PVC, PE, and
Testis KOH Fiber, subspherical 20~100 µm, [36]
Py-GC/MS PP
11.60 ± 15.52 particles/g
PVA, PVC, PP, Fragments/irregular 4 pigmented MPs
Urine KOH µRaman [37]
and PE MPs shape fragments 4~15 µm
Py-GC/MS: pyrolysis-gas chromatography/mass spectrometry; LD-IR: Laser Desorption-Infrared Spectroscopy;
SEM: Scanning electron microscopy; µRaman: Raman Microspectroscopy; µFTIR: Fourier Transform Infrared
micro-spectroscopy; PET: polyethylene terephthalate; PE: polyethylene; PU: polyurethane; PMMA: poly(methyl
methacrylate); PA: polyamide; PP: polypropylene; PVC: polyvinyl chloride; PC: polycarbonate; PS: polystyrene;
PBS: polybutylene succinate; PSF: polysulfone; KOH: potassium hydroxide; NaHOCl: Sodium hypochlorite;
HNO3 : nitric acid; NaOH: Sodium hydroxide; ZnCl2 : Zinc chloride; H2 O2 : hydrogen peroxide. + : Quantity is
based on maximum concentration detected in the study; ++ : samples were pre- and postoperative blood samples.

2.1. MPs in Human Liver, Kidney and Spleen


The human liver, kidney, and spleen are crucial organs for overall health. The liver,
located in the right abdomen, detoxifies the blood, aids in digestion, regulates blood sugar,
and produces clotting proteins. Kidneys, positioned on either side of the spine, filter
waste, regulate fluid balance, blood pressure, and activate vitamin D. The spleen, found
on the left side behind the stomach, serves immune functions, filters blood, and stores
essential blood components, helping fight infections caused by bacteria [39–44]. These three
organs, the liver, kidneys, and spleen, work in harmony to maintain the body’s internal
balance, support immune function, and ensure proper waste elimination. Caring for these
organs through a balanced diet, regular exercise, and avoiding harmful substances can help
Environments 2023, 10, 194 4 of 18

promote overall health and well-being. However, they have been faced with contamination
by MPs [31]. In Horvatits et al. [31], tissue samples from six patients with liver cirrhosis
and five healthy subjects were compared. 17 samples in all, comprising 11 liver samples,
3 kidney samples, and 3 spleen samples, were examined. The scientists used a well-known
methodology to find MPs particles in human tissue that were between 4 and 30 µm in
size. The tissue samples were chemically digested as part of this technique, then they were
stained with Nile red. The properties and make-up of the MPs were further evaluated
using µRaman and fluorescence microscopy.
According to the findings, liver, kidney, and spleen samples from healthy people did
not contain any MPs when compared to the limit of detection. In contrast, cirrhosis-affected
liver tissues revealed positive MPs quantities that were significantly greater than liver
samples from people without liver disease. The research discovered six different kinds of
MPs polymers [PS, PVC, PET, PMMA, POM, and PP] in the cirrhotic liver tissues, ranging
in size from 4 to 30 µm.
These results highlight the existence of MPs in cirrhotic liver tissues and their much
greater quantities as compared to healthy persons. Additionally, the identification of
distinct MPs offers important new information on the make-up of MPs in relation to liver
cirrhosis. However, in animal studies, research [45] has confirmed the accumulation of PS
NPs in the liver and kidneys of mice, leading to noticeable structural and functional changes
in these organs. In a related study [46], the inflammatory impact of PS NPs of varying sizes
(100 and 50 nm) and PS MPs on transgenic zebrafish larvae was investigated. Smaller NPs
were found to provoke higher levels of neutrophil aggregation and macrophage apoptosis
in the larvae’s abdomen, correlating with increased hepatic inflammation. Furthermore,
NPs were observed to dose- and size-dependently enhance the expression of the liver-
specific inflammatory binding protein fabp10a. The 50 nm PS particles at a concentration
of 0.1 mg/L increased fabp10a expression in larval livers by 21.90%. The authors propose
that these effects are contingent on NP distribution and the generation of reactive oxygen
species within the larvae. These findings deepen our comprehension of the possible effects
of MPs pollution on liver function and emphasize the value of more studies in this area to
fully comprehend the effects of MPs pollution on human health.

2.2. MPs in Human Blood


Blood, a crucial bodily fluid, plays a crucial function in preserving general health. It
offers a great matrix for looking at plastic particles through human biomonitoring as a
result of its function as a transport route and its capability to take blood samples directly
from the body without interaction with plastic materials.
In light of these elements, research was carried out to examine the presence of plastic
particles in blood and their possible effects on human health [30]. This study provided the
first evidence of MPs in blood. The extent of plastic pollution and its effects on the human
body were investigated through the analysis of blood samples.
A double shot Py-GC/MS analytical and sampling method that was precise and sensi-
tive to assessed MPs in blood was developed by Leslie et al. [30]. Quantification of MPs
(≤700 nm) or less was performed on whole blood samples from 22 healthy persons. PET
was the most commonly encountered polymer, with quantifiable values found in 50% of
all tested donors. Following these were PMMA (5%), PE (23%), and PS (36%). The blood
samples had maximal concentrations of PET, PS, and PE of 2.4 µg/mL, 4.8 µg/mL, and
7.1 µg/mL, respectively. Based on a limited number of donors, this study offers a unique
way to assess the bulk concentration of plastic particles in human blood. The polymeric
component of plastic in the blood was found to be present at a mean total measurable
concentration of 1.6 µg/mL. Their results demonstrated the presence of different plastic
particles in human blood, demonstrating the possibility of bloodstream exposure to MPs.
Since there is no information on the long-term health impacts of MPs in human blood,
further study is required to better comprehend the dangers. This entails examining the
origins and routes by which MPs enters the bloodstream, looking into the distribution and
Environments 2023, 10, 194 5 of 18

accumulation trends, and determining how they could affect various physiological and
cardiovascular systems as well as immunological responses and other aspects of human
health. In a recent investigation conducted by Yang et al. [32], a comprehensive analysis of
venous blood samples taken before and after cardiac surgery revealed a consistent presence
of MPs across all samples, with sizes spanning from 20 to 184 µm. Notably, the most
prevalent types of MPs were identified as PA (49%) and PET (22%), collectively constituting
over 70% of the total microplastic content. The study also unveiled concerning fluctuations
in the composition of MPs before and after surgery. For instance, PET dominated the
pre-surgery blood samples, accounting for 67% of the total MPs, while PA took precedence
in the post-surgery samples, making up 57%. The researchers identified eight distinct
types of MPs in the post-surgery blood samples, in contrast to the six types detected in
the pre-surgery blood samples. Remarkably, the prevailing diameter range of MPs shifted
between the pre- and post-surgery phases. Before the surgery, MPs primarily fell within
the 30 to 50 µm diameter range (67%), while after the surgery, a smaller diameter range
prevailed (20 to 30 µm, 51%). These findings have notable implications for both human
health and environmental awareness. The consistent presence of MPs in the bloodstream,
along with the discernible shifts in MPs’ composition and diameter range following cardiac
surgery, underscores the potential interaction between medical interventions and MPs
exposure. The prevalence of these synthetic particles, particularly those of PA and PET
origins, raises questions about their potential impact on postoperative recovery and cardio-
vascular health. Furthermore, the dynamic alterations in MPs characteristics emphasize
the intricate relationship between medical procedures and the body’s response to plastic
pollution. As research in this domain continues to unfold, it becomes imperative to com-
prehensively address the implications of MPs in the context of medical practices and their
broader consequences on human well-being and the environment.

2.3. MPs in Human Heart


MPs in the human heart have emerged as a concerning and relatively novel topic of
research in recent. One study published identified MPs in human heart for the first time [32].
To present conclusive evidence of MPs’ presence within the human heart, Yang et al. [32]
conducted a study involving 15 patients undergoing cardiac surgeries in China. These
individuals, devoid of any thoracic surgery or trauma history, generously contributed
their tissue samples. Thirteen patients exhibited normal alanine aminotransferase (ALT)
and serum creatinine (Scr) values, while two showed anomalies in ALT and Scr levels. In
their investigation, Yang and his team meticulously gathered five distinct types of normal
tissue samples: pericardia, epicardial adipose tissue (EAT), pericardial adipose tissue (PAT),
myocardia, and left atrial appendage (LAA), based on surgical type and patients’ nutritional
status (Figure 1).
The researchers successfully identified nine categories of MPs (Table 1), with PET
(77%) and PU (12%) prevailing as the most common, constituting nearly 90% of the overall
MPs content. Curiously, PE was present across all tissue samples, despite comprising only
1% of the total microplastic count. Interestingly, MPs were absent in two pericardium
samples, one myocardium sample, two EAT samples, and five PAT samples. Furthermore,
PET dominated as the primary microplastic type in the pericardium (96%), EAT (83%),
PAT (49%), and myocardium (43%, equivalent to PA), while PU was prominent in the LAA
(43%). Notably, the pericardium, PAT, and LAA exhibited the greatest variety of MPs types
(7 types), followed by EAT (6 types). Most MPs detected in heart samples possessed a
diameter below 100 µm (Figure 1b), with a general diameter range spanning from 20 to
469 µm. Moreover, scanning electron microscopy (SEM) images disclosed diverse in vivo
MPs shapes, encompassing threads and rods, often accompanied by varying degrees of
fracture and surface roughness (Figure 1c,d).
Environments 2023, 10, x FOR PEER REVIEW 6 of 1
Environments 2023, 10, 194 6 of 18

Figure 1. (a) Part of the heart collected and analyzed for MPs; (b) distribution MPs based on sizes on
Figure 1. (a)heart
different Partparts
of the heart collected
analyzed; and analyzed
(c,d) representative samplesfor MPs;found
of MPs (b) distribution MPs based
under SEM (adapted with on size
on different heart parts
permission from [32]). analyzed; (c,d) representative samples of MPs found under SEM (adapted
with permission from [32]).
The implications of these findings remain substantial, as they underscore the per-
The researchers
vasive presence of MPs successfully
within theidentified nine categories
human cardiovascular system.of MPs (Table 1),the
Understanding with PET
(77%) and PU (12%) prevailing as the most common, constituting nearly 90% of the overal
sources, potential health effects, and routes of entry for these microscopic plastic particles
into our bodies holds significant importance for both human health and environmental
MPspreservation
content. Curiously,
endeavors.
PE was present across all tissue samples, despite comprising only
1% of the total microplastic
However, a recent overview count. Interestingly,
of research MPs
on the effects were(MPs)
of MPs absentand in
NPs two
(NPs)pericardium
on
samples, one myocardium
the cardiac sample,
physiology of aquatic two EAT
species samples,[47].
was published and When
five PAT
eaten samples. Furthermore
at 120 mg/mL,
PETPS-NPs
dominated as the impact
had a negative primary microplastic
on heart type in
rate in zebrafish the and
larvae pericardium
embryos from (96%), EAT (83%)
maternal
PAT (49%), and myocardium (43%, equivalent to PA), while PU was prominent in the LAA
and/or co-parental exposure groups due to their interaction with the cardiac sarcom-
eres [48]. In a different research on zebrafish larvae, PS-NP was only localised in the
(43%). Notably, the pericardium, PAT, and LAA exhibited the greatest variety of MP
pericardium at the highest dose of 10 ppm [49]. In this study, after 24 h of egg fertilization,
types (7 types), followed by EAT (6 types). Most MPs detected in heart samples possessed
PS-NPs that had been exposed to water gathered in the yolk sac and moved to the devel-
a diameter below
oping heart, 100 µm (Figure
gastrointestinal system,1b), with a general
gallbladder, diameter
liver, pancreas, andrange
brain spanning
in additionfrom
to 20 to
469 other
µm. Moreover, scanning
organs. Notably, exposed electron microscopy
groups displayed (SEM)bradycardia
significant images disclosed diverse
in comparison to in vivo
MPscontrols
shapes, encompassing
even threads
at the lowest PS-NP dosesand rods,
of 0.1 ppm often
[49]. accompanied
Another researchby varying
[50] degrees o
confirmed
fracture and surface roughness (Figure 1c,d).
that marine medaka pups exposed to 20 g/L PS-MPs from their parents had a considerable
reduction in heart rate. Along with hypothetical particle interactions with cardiac sarcom-
The implications of these findings remain substantial, as they underscore the perva
eres, the oxidative state produced by MPs may also have an impact on heart rate. However,
siveeven
presence of MPs
at low doses within
(10 g/L; 100 andthe1000
human
g/L were cardiovascular system. (medical
also tested), tachycardia Understanding
term the
sources, potential
for a heart health
rate >100 beatseffects, and routes
per minute) of entry
was observed for these
in goldfish microscopic
larvae exposed toplastic
PS-MPsparticles
intoand
our-NPs
bodies holds significant
combination after 7 days importance
of treatment [51].for These
both human
contrastinghealth
effectsand environmenta
on aberrant
preservation endeavors.
heart rate may be caused by this organ’s vulnerability to the oxidative stress brought on
However, a recent overview of research on the effects of MPs (MPs) and NPs (NPs
on the cardiac physiology of aquatic species was published [47]. When eaten at 120
mg/mL, PS-NPs had a negative impact on heart rate in zebrafish larvae and embryos from
maternal and/or co-parental exposure groups due to their interaction with the cardiac sar
Environments 2023, 10, 194 7 of 18

by the body’s entrance of toxic plastics. These studies suggest that MPs can interfere with
normal cardiac function, potentially contributing to cardiovascular diseases in humans.
Studies are required to fill this knowledge gap.

2.4. MPs in Human Placenta


During pregnancy, a crucial organ called the placenta develops in the uterus [52]. It
starts forming about seven to ten days after conception when a fertilized egg implants in the
uterine wall [52]. Throughout pregnancy, the placenta continuously expands to support the
growing baby, providing oxygen and nutrients while also eliminating waste products from
the baby’s blood [53]. However, placenta faces a plastic problem as it has been reported
to be contaminated by MPs [33]. In Ragusa et al. [33], MPs were detected in human
placenta. Using µRaman, they examined placentas collected from consenting patients,
with an average weight of 23.3 ± 5.7 g. Approximately 600 g of the placenta was used for
analysis. They identified 12 MP pieces, primarily composed of PP, with sizes ranging from
approximately 5 to 10 µm in the placentas of four women. Interestingly, MPs were found in
various sections of the placenta, including the maternal side, fetal side, and chorioamniotic
membranes, suggesting that these particles may reach placenta tissues at all levels once
inside the human body. In a different research, PVC (43.27%), PP (14.55%), and PBS (10.90%)
were the three primary polymer types (from 11 types) discovered in the placenta, according
to Zhu et al. [38]. These MPs had diameters ranging from 20.34 to 307.29 µm, with the
majority (80.29%) being less than 100 µm, and an abundance of 2.70 ± 2.65 particles/g on
average, with a range of 0.28 to 9.55 particles/g.
The immunological mechanism of self-tolerance has to be reconsidered in light of
the presence of MPs in the placenta tissue. The placenta serves as the link between the
foetus and its surroundings [53]. Through a series of intricate reactions, embryos and
foetuses must constantly adjust to the maternal environment and, in turn, the external
one. This set of reactions depend heavily on the ability to distinguish between self and
non-self, a system that can be compromised by the presence of MPs. In fact, it has been
suggested that MPs, if ingested by humans, may accumulate and cause localised toxicity
by triggering and/or increasing immunological responses, thereby weakening the body’s
defences against infections and changing how energy reserves are used [20,54]. Further
studies are required to explicitly identify the toxicity these MPs pose within the placenta
and risks to the foetus. In a research by Enyoh et al. [55], the toxicity of 10 different kinds
of NPs on the placenta was investigated utilising in silico and machine learning techniques.
The placenta plays a critical role in metabolic and excretion processes through its enzymatic
system, hence the researchers concentrated on evaluating the inhibition of placental en-
zymes by these NPs. The soluble epoxide hydrolase, uracil phosphoribosyltransferase, beta
1,3-glucuronyltransferase I, sulfotransferase, N-acetyltransferase 2, and cytochrome P450
1A1 were among the human enzymes involved in placental function that the NPs were
docked onto in the research. The binding affinity-based toxicity was then contrasted with
control substances. Artificial Neural Networks were utilised to predict toxicity based on
these reactivity descriptors after density functional theory analysis of the NPs was carried
out to determine their global reactivity descriptors. According to the findings, the most
hazardous polymers are PC, PET, and PS, which all exhibit the greatest levels of toxicity to
all enzymes. A fractional factorial design technique and a fixed effects model were used
to evaluate the impact of NPs in a composite system. The simulation’s findings indicated
that a combination of NPs may seriously endanger the placenta by blocking important
enzymes. This work sheds light on the possible dangers of exposure to plastic particles
during pregnancy and their effects on placental function by highlighting the potential
toxicity of certain NPs to placental enzymes.
Environments 2023, 10, 194 8 of 18

2.5. MPs in Breast Milk


Breast milk often called as the ‘liquid gold’, not only due to its yellow or orange
color, but also as it’s a vital source of nutrition and protection for the new born baby [56].
Breast milk contains millions of live cells, significant amount of protein, over two hundred
complex sugars called oligosaccharides, and more than forty enzymes that are critical
micronutrients for the growth and development of a baby [57].
Recently, Ragusa et al. [34] have found MPs in the milk produced by a female human
breast, which is apparently a matter of great concern. In their study breast milk of 34 women
were collected after a week of delivery, each sample contained on an average of 4.16 gm
of milk and was stored at −20 ◦ C. Surprisingly the MP particles were found in 26 out of
34 women samples. MPs are further classified in terms of shape, size, colour, dimensions
and chemical compositions. In terms of shape and colour, nearly all MPs were found as
blue or orange/yellow spherical or irregular fragments with dimensions ranging between
2 and 12 µm. Within the identified polymer matrices, the most abundant ones were PE
(38%), PP (38%), and PVC (17%).
For a new born early years are both crucial and sensitive, it’s where the physical
and mental growth are at peak and the only source of immunity and nutrition to them
is their mother’s milk. When the very elixir of their lives begins to sustain impurities
such as MPs, there occurs a need for urgent attention. However, the adverse effects are
yet to be discovered, but that does not necessarily decrease the risk level. In light of
these, Enyoh et al. [58] conducted a computational simulation to assess the risks posed
by small plastic particles (including PS, PVC, PUR, PMMA, PET, PE, PP, PCP, and PC) in
breast milk to newborns, potentially affecting the levels of secretory immunoglobulin A
(SIgA). SIgA is a crucial antibody that plays a vital role in protecting against diseases and
contributes to the development of the infant’s immune system [59]. The study revealed that
PC (polycarbonate) was found to be considerably toxic, whereas the other plastic particles
showed moderate toxicity. These findings highlight the potential risks associated with the
presence of these plastic particles in breast milk, impacting the immunity of infants.
Understanding how MPs enter breast milk and the potential risks they pose will be
essential in developing strategies to reduce exposure and protect infant health. As such,
future perspectives in this area include conducting comprehensive studies on the presence
and concentration of MPs in breast milk from different populations, investigating any
potential short-term or long-term health impacts on breastfeeding infants, and exploring
ways to mitigate MPs exposure for both lactating mothers and infants.

2.6. MPs in Sputum


The mucus or phlegm that is coughed up from the respiratory tract, especially the
lungs and bronchi, is known as sputum. Saliva, nasal secretions, and materials made by
the respiratory system, such as mucus and cells, are all included in its composition [60].
Depending on the underlying illness or infection, the colour, consistency, and smell of
sputum might change [60]. As a possible route for human MP intake, sputum is now
being examined for the existence of MPs [35]. Huang et al. [35] tested human sputum
for MPs (20-500 µm) using samples collected from 22 patients with diverse respiratory
conditions to ascertain whether people unwittingly inhale MPs. Participants had to submit
a questionnaire and sputum samples for examination. To determine if MPs were present
in the respiratory tract, sputum samples were analyzed using an FTIR microscope and a
laser infrared imaging spectrometer. According to their findings, 21 distinct MP types were
found in the sputum samples, with PUR being the most prevalent. Polyester, chlorinated
polyethylene, and alkyd varnish were next, making up 78.36% of all of the MPs found.
MPs are abundant in sputum samples, according to the results of this study, indicating
that inhalation may be a key way for plastics to enter the human body. Furthermore, with
statistical significance (p < 0.05), it was shown that the levels of specific types of MPs
identified in the respiratory tract were related to a number of characteristics, including
smoking and invasive medical procedures, among others. These results offer important
Environments 2023, 10, 194 9 of 18

new information on MPs exposure and give crucial information for evaluating the possible
dangers of MPs to human health.

2.7. MPs in Testis and Semen


The male reproductive system is a complex network of organs and tissues responsible
for the production, storage, and distribution of sperm, which significantly impacts fertility
and overall reproductive health [61]. This system comprises two main components: the
testes, responsible for sperm cell production through spermatogenesis, and semen, which
includes sperm cells and other seminal fluid components necessary for their survival and
motility [61]. Recently, researchers have turned their attention to investigating the potential
presence and harmful effects of MPs (MPs) within the male reproductive system. A study
by Zhao et al. [36] reported the discovery of MPs in human testis and semen. In this study,
two groups of samples were collected: the first group included 5 semen samples analyzed
using Py-GC/MS for MP analysis, and the second group comprised 25 semen samples and
6 testis samples analyzed using LD-IR for MP analysis. The results of the LD-IR analysis
indicated that semen had an average MP abundance of 0.23 ± 0.45 (ranging from 0 to 2.06)
particles per milliliter. This abundance was lower compared to the MP levels found in
sputum samples [35]. Similarly, using Py-GC/MS analysis, MPs were detected in semen
samples from 5 individuals, with an average abundance of 15.34 ± 23.31 (ranging from
0.098 to 56.188) mg/mL. Regarding morphology, the identified MPs in semen comprised
approximately 29% fibers, 29% fragments, 29% films, and 13% subspherical particles, with
sizes ranging between 21.76 and 286.71 (average of 96.19 ± 74.17) micrometers. Notably,
67% and 80.6% of the particles found in human testis and semen, respectively, were MPs
with sizes between 20 and 100 micrometers. Among the MPs identified, PVC and PE
were more prevalent in testis than PS. Additionally, the MPs found in the testis were
significantly smaller than those observed in semen, aligning with the hypothesis proposed
by Zhao et al. [36] that larger MPs are expelled or found in the external contact fraction,
while smaller MPs tend to accumulate in vivo. These findings provide important insights
into the presence and characteristics of MPs in human semen and testis. The prevalence of
specific MP types and their size distributions in these reproductive samples warrant further
investigation to understand their potential implications for male reproductive health and
fertility. Animal studies have demonstrated that exposure to MPs can lead to decreased
sperm quality, altered hormone levels, testicular inflammation, and impaired fertility [62].
For instance, the Nrf2/HO-1/NF-κB be activated by exposure to polystyrene MPs (PS-MPs)
and disrupt the testicular tissue of mice, leading to poor sperm quality [63]. Additionally,
PS-MPs can drastically inhibit follicle formation in rats and result in granulosa cell death,
which reduces ovarian reserve capacity and harms the ovaries via activating the Wnt/β-
Catenin pathway [64]. It has also been demonstrated that accumulation of PS-MPs of 0.5, 4,
and 10 µm may occur in mouse testicular tissue, leading to the shedding of seminiferous
epithelial cells and rupturing of the blood-testis barrier.
According to earlier research, exposure to PS-MPs can also cause aberrant growth
of germ cells in male Japanese medaka [65] and lower the number of sperm in oys-
ters [66]. Mammals’ sperm quality and quantity are declining, and this is particularly
true of mice [67]. There is, however, a paucity of information and research about MPs on
male reproduction and its underlying harmful mechanism as a new persistent pollutant.
Multiple signaling pathways are engaged with MPs, and as strongly confirmed by other
research [68,69], oxidative stress is seen as a primary and prominent harmful mechanism.
According to Wang et al. [50], oxidative stress is characterized by rising levels of malondi-
aldehyde (MDA) and falling levels of superoxide dismutase (SOD), catalase (CAT), and
glutathione peroxidase (GSH-PX), which is a relative oxygen species (ROS) producer. In the
meantime, it has been shown that exposure to PS-MPs in mice testis increases ROS and MDA
levels while decreasing glutathione (GSH) levels, indicating that the p38 mitogen-activated
protein kinases (MAPK) pathway is activated [70]. Furthermore, prior research has unequiv-
ocally confirmed the direct link between Bric-a-Brac/Tramtrack/Broad-complex protein
Environments 2023, 10, 194 10 of 18

(BTB) deficiency and p38 pathway activation. BTB are a family of transcription factors or
co-regulators involved in gene regulation Betaine has protective effects on BTB through
downregulating the expressions of p38 MAPK phosphorylation [71], and BTB might be
damaged by activating the TGF-3/p38 MAPK pathway in rats [72]. It is yet unknown,
nevertheless, whether MPs exposure through the p38 MAPK pathway might cause BTB
impairment. Male reproduction and spermatogenesis depend on the health of the BTB
ultrastructure. Tight junctions (TJs), gap junctions (GJs), basal ectoplasmic specialization
(ESs), and desmosomes make up the BTB, which is a physical barrier created by Sertoli
cells (SCs) between blood arteries and testicular seminiferous tubules [73]. In addition to
serving as a source of nutrients, BTB also serves as a crucial physical barrier and immune-
privileged location that can block the entry of hazardous and damaging pollutants, creating
a favorable microenvironment for spermatogenesis [73]. For maintaining male reproductive
function, proper spermatogenesis is unquestionably important. Therefore, spermatogenesis
can be disturbed by the disruption of BTB normal structure, which can then result in a
reproductive problem in male mammals. Literature on the impact of MPs on BTB is still
only occasionally documented, though. According to a newly released study, mice’s BTB
could potentially be damaged by 0.5 µm PS-MPs absorbed by Sertoli cells [70]. However,
the chemical process underlying it is still not fully understood. Moreover, the physical
and chemical properties of MPs, such as their small size, large surface area, and ability to
adsorb and release toxic chemicals, raise concerns about their potential to disrupt hormonal
balance and interfere with cellular processes within the testes. As the scientific commu-
nity continues to investigate the impacts of MPs on male reproductive health, it is crucial
to explore the mechanisms through which MPs exert their effects and identify potential
long-term consequences. Further research is needed to determine the extent of human
exposure to MPs, understand their distribution and accumulation patterns within the male
reproductive system, and elucidate the mechanisms by which they may impact sperm
function, fertility, and overall reproductive health.

2.8. MPs in Urine


Human urine is a liquid waste product excreted by the kidneys as part of the body’s
process of filtering and eliminating waste materials from the bloodstream. It is a transparent
to pale-yellow fluid that varies in color depending on an individual’s hydration levels
and dietary intake. Urine is composed of approximately 95% water, making it an essential
component of the body’s waste removal system [74]. The characteristics of urine, such as
color, odor, and frequency of urination, can provide valuable insights into an individual’s
hydration status and overall health [74].
There is a paucity of studies investigating the presence of MPs in human urine and
their potential implications for human health. A notable study by Pironti et al. [37] shed
light on this topic by examining urine samples from six volunteers residing in various cities
in southern Italy. The researchers utilized µRaman to analyze the samples and identify MPs.
The results of the analysis revealed the existence of four pigmented microplastic fragments,
ranging in size from 4 to 15 micrometers, with irregular shapes [37]. The researchers further
investigated the morphology and chemical composition of these MPs. Specifically, they
identified the presence of polyethylene vinyl acetate (PVA), polyvinyl chloride (PVC), PP,
and polyethylene (PE) MPs in the samples. Interestingly, one female sample contained both
PVA and PVC MPs, while three male samples contained PP and PE MPs (Figure 2).
These findings offer preliminary evidence suggesting that MPs may be able to traverse
the gastrointestinal tract and be expelled from the body through biological processes,
ultimately appearing in urine. Such research is crucial as it provides valuable insights
into the potential pathways of MPs exposure in humans and opens up new avenues for
investigating their health implications. Further studies are warranted to comprehensively
understand the extent and impact of microplastic presence in human urine.
Environments 2023, 10, x FOR PEER REVIEW 11 of 1

Environments 2023, 10, 194 sample contained both PVA and PVC MPs, while three male samples contained
11 of 18 PP and
PE MPs (Figure 2).

(a)

(b)
Figure 2. Samples
Figure 2. SamplesofofMPs
MPsunder themicroscope
under the microscope andand µRaman
µRaman spectra
spectra found found
in urineinofurine of and
(a) male (a) male and
(b) female (Adapted
(b) female (Adaptedwith
with permission from
permission from [37]).
[37]).

3. Plausible Pathways of MPs to Different Organs and Bodily Fluids


These findings offer preliminary evidence suggesting that MPs may be able to trav
An overview of the plausible pathways of MPs to different organs and bodily fluids
erse the gastrointestinal tract and be expelled from the body through biological processes
is presented in Figure 3. MPs may enter the circulation by a variety of routes, such as
ultimately
ingesting,appearing in urine.
inhaling, and Suchabsorption.
cutaneous research is Once
crucial as it the
within provides valuable
body, they insights into
may build
the up
potential pathways
in the digestive of MPs
system. exposure
Given that MPsinare
humans andpresent
frequently opens up new avenues
in seafood, for inves
drinking
tigating their health implications. Further studies are warranted to comprehensively un
water, and even the air we breathe, studies indicate that ingestion is the primary method
derstand
by whichthethey
extent and
enter the impact of Smaller
body [75]. microplastic presence
particles can enterinthehuman urine.once they
bloodstream
reach the gastrointestinal tract through: (1) permeability, where MPs may pass through
the intestinal epithelium due to its porous nature, as MPs have been observed in human
3. Plausible Pathways of MPs to Different Organs and Bodily Fluids
colectomy samples [76]; (2) MPs may be transported through the lymphatic system, which
is An overview
involved of thecell
in immune plausible
transportpathways of MPs of
and the absorption tofats
different organs
[77]; and and
(3) from thebodily
liver, fluid
is presented in Figure 3. MPs may enter the circulation by a variety of routes, such a
which turns nitrogenous waste into urea, a less harmful compound. The circulation receives
ingesting,
urea onceinhaling, and
liver cells cutaneous
release absorption.
it [78]. As a result, MPs Once
couldwithin
enter the body, they may
the bloodstream. Frombuild up
the bloodstream, MPs can potentially be distributed to various organs and tissues, such as
in the digestive system. Given that MPs are frequently present in seafood, drinking water
breast milk, heart, placenta, sputum, semen, testis and urine (Figure 3).
and even the air we breathe, studies indicate that ingestion is the primary method by
which they enter the body [75]. Smaller particles can enter the bloodstream once they
reach the gastrointestinal tract through: (1) permeability, where MPs may pass through
the intestinal epithelium due to its porous nature, as MPs have been observed in human
colectomy samples [76]; (2) MPs may be transported through the lymphatic system, which
is involved in immune cell transport and the absorption of fats [77]; and (3) from the liver
which turns nitrogenous waste into urea, a less harmful compound. The circulation re
ceives urea once liver cells release it [78]. As a result, MPs could enter the bloodstream
Environments 2023, 10, x FOR PEER REVIEW 12 of 18

Environments 2023, 10, 194 From the bloodstream, MPs can potentially be distributed to various organs and tissues,
12 of 18
such as breast milk, heart, placenta, sputum, semen, testis and urine (Figure 3).

Figure
Figure 3. An
3. An overviewofofthe
overview theplausible
plausiblepathways
pathways of of MPs
MPs to
to different
differentorgans
organsand
andbodily
bodilyfluids. Intake
fluids. Intake
of MPs
of MPs areare possible
possible via
via inhalation,ingestion
inhalation, ingestion and and skin
skin contact.
contact. Once
Onceininthe
thebody,
body,they
theyare
areabsorbed
absorbed
intointo
thethe gastrointestinal
gastrointestinal tractfrom
tract fromwhich
whichititisistransported
transported to
to the
the bloodstream.
bloodstream.The
Thebloodstream
bloodstream then
then
circulates it to the different internal organs and then potentially excreted via the urine and semen.
circulates it to the different internal organs and then potentially excreted via the urine and semen.
According to one theory, MPs move from the circulation into breast milk via two
According to one theory, MPs move from the circulation into breast milk via two
different paths, each of which depends on immune cells and mammary epithelial cells,
different paths, each of which depends on immune cells and mammary epithelial cells,
with the la er being particularly important for inhaled particles [34]. The major cells in
with the latter being particularly important for inhaled particles [34]. The major cells
charge of generating and secreting breast milk are mammary epithelial cells. These cells
in charge of generating and secreting breast milk are mammary epithelial cells. These
go through particular physiological changes during lactation in order to produce and
cells go through particular physiological changes during lactation in order to produce
transport different substances, such as proteins, lipids, and carbohydrates, into breast
and transport different substances, such as proteins, lipids, and carbohydrates, into breast
milk [79]. According to the theory, during this secretion phase MPs can be picked up by
milk [79]. According to the theory, during this secretion phase MPs can be picked up by
mammary epithelial cells and then released into the breast milk. One potential explana-
mammary
tion is thatepithelial
MPs may cells
be and then released
recognised by certainintoreceptors
the breastonmilk. One potential
the surface explanation
of mammary epi-
is that MPs may be recognised by certain receptors on the surface
thelial cells once they have entered the circulation or interstitial fluid surrounding of mammary epithelial
the
cells once they
mammary have entered
glands. When the the circulation
MPs are takenor upinterstitial
by vesiclesfluid
and surrounding
carried into thethecytoplasm
mammary
glands.
of the When the MPs areknown
cell, a mechanism taken as upreceptor-mediated
by vesicles and carried into may
endocytosis the cytoplasm
be used byofthe the
cell,
cells to internalise the MPs [80]. Once within the cell, the MPs could be contained in milkto
a mechanism known as receptor-mediated endocytosis may be used by the cells
secretorythe
internalise vesicles
MPs [80].and discharged
Once withinduring lactation
the cell, the MPs into the mother’s
could milk.inPassive
be contained diffu-
milk secretory
sion isand
vesicles another possible
discharged process.
during MPs could
lactation into the diffuse
mother’sinto milk.
the cells and then
Passive be delivered
diffusion is another
to milkprocess.
possible secretory MPsvesicles
could if diffuse
their size andthe
into chemical
cells and makeup
then beenable them to pass
delivered milk past the
secretory
cellular
vesicles membranes
if their size and of chemical
mammary epithelial
makeup cells.them
enable The second
to passroute
past involves immune
the cellular cells
membranes
such as macrophages,
of mammary epithelial cells. whichTheare foundroute
second in breast tissueimmune
involves and assist insuch
cells immunological de-
as macrophages,
fence by phagocytosing and eliminating foreign substances and debris from the lungs
which are found in breast tissue and assist in immunological defence by phagocytosing
and[81]. Including foreign
eliminating MPs, these foreign particles
substances and debris allowfromfor the
engulfment andIncluding
lungs [81]. internalisation. Af-
MPs, these
ter being
foreign takenallow
particles up byfor immune
engulfmentcells and
in the lungs, MPs can
internalisation. thenbeing
After movetaken
via the
uplymphatic
by immune
system
cells in theorlungs,
circulation
MPs until theymove
can then reach viathe breast tissue, where
the lymphatic systemthey
ormay be released
circulation untilinto
they
breast
reach themilk
breastduring
tissue, lactation.
where they may be released into breast milk during lactation.
It is
It is importanttotoremember
important rememberthat thatthethe actual
actual processes
processes maymaybe bemore
morecomplicated
complicated than
than
those
those proposed,and
proposed, andthat
thatthe
theconcept
concept of of MPs
MPs translocating
translocating to tobreast
breastmilk
milkthrough
throughthese
these
routes
routes is is still
still ananactive
activearea
areaofofresearch.
research. The The MPs’
MPs’ precise
precise dimensions,
dimensions,make-up,
make-up,and and
interactions with diverse cells and tissues might have an impact on the translocation
process. The quantity and presence of MPs in breast milk may also depend on additional
variables such exposure levels, length of exposure, and individual variances.
In the case of the heart, it may take place as a result of MPs penetrating the blood
channel endothelial cells. Additionally, MPs can cause oxidative stress and inflammation,
which can cause the blood vessel barrier to rupture and let MPs into the heart tissue [32].
Environments 2023, 10, 194 13 of 18

MPs can cross the placental barrier after entering the mother’s circulation and go to the
foetal side [55]. During pregnancy, a unique structure called the placental barrier divides
the maternal blood supply from the foetal blood supply [55]. Its primary job is to defend
against hazardous chemicals while facilitating the flow of gases, nutrients, and other vital
substances. Syncytiotrophoblast, the placenta’s outermost layer, foetal endothelial cells, and
other supporting tissues make up the placental barrier’s many layers [82]. Theoretically,
there are two ways that MPs might traverse the placental barrier: (1) through microscopic
holes or breaches in the barrier, which may also be created by inflammation and barrier
disruption; (2) by endocytosis, in which MPs are taken up by cells and transported over
the barrier; and (3) immunological cells can also transfer MPs through the barrier as
part of immunological reactions. To completely comprehend the methods and degree of
microplastic transfer to the placenta, more studies are necessary.
However, factors such as their elimination by renal filtration or biliary excretion,
or their deposit in organs such as the liver, spleen, or other fenestrated capillaries and
sinusoids, dictate the fate of plastic particles inside the body [30]. Sputum can also be
used for elimination in the respiratory system. Nitrogenous waste must first be changed
by the liver into a less dangerous molecule before being released from liver cells into the
circulation and finally to the kidney [78]. Although the renal excretion may be a viable
pathway for the removal of MPs, it is known that the glomerular filtration barrier only
permits the transit of particles with sizes of 10 nm. The mechanism for this may involve
exocytosis and endocytosis close to the tubular epithelial cells after leaving the glomerulus
via the efferent artery and entering the peritubular capillaries, before the MPs are excreted
into the urine [37]. MPs can also pass through the renal tubule system, though this is less
common [37].
As the testes have a rich blood supply, it is possible that some MPs circulating in
the blood could reach the testicular tissue which include a barrier (blood-testis barrier)
(Figure 4). The testes are protected by this specialized barrier, which also helps to maintain
a stable internal environment for spermatogenesis and protects developing sperm from
harmful substances in the blood. However, some studies have suggested14that
Environments 2023, 10, x FOR PEER REVIEW of 18certain
toxicants may be able to disturb this barrier [83] and thus form a pathway of MPs reaching
the testes.

Blood

Direct contact

Figure 4. Plausible
Figure pathways
4. Plausible of MPsofinto
pathways MPstheinto
testes.
the(A) is showing
testes. (A) isthe specific location
showing of thelocation
the specific blood- of the
testes barriers while
blood-testes (B) iswhile
barriers unraveling the cellular the
(B) is unraveling composition and intricate structure
cellular composition of the
and intricate blood- of the
structure
testis barrier, while exploring the supportive role of neighboring cells in maintaining barrier func-
blood-testis barrier, while exploring the supportive role of neighboring cells in maintaining barrier
tion and balance (Adapted with permission and modification from ref. [83]).
function and balance (Adapted with permission and modification from ref. [83]).
The lymphatic system is another potential pathway through which MPs could reach
the testes. The lymphatic system is a network of vessels and organs that helps to transport
lymph, a fluid containing white blood cells, throughout the body [84]. MPs may be taken
up by immune cells in the lymphatic system and transported to different tissues, including
the testes. However, in some cases, MPs may come into direct contact with the male re-
Environments 2023, 10, 194 14 of 18

The lymphatic system is another potential pathway through which MPs could reach
the testes. The lymphatic system is a network of vessels and organs that helps to transport
lymph, a fluid containing white blood cells, throughout the body [84]. MPs may be
taken up by immune cells in the lymphatic system and transported to different tissues,
including the testes. However, in some cases, MPs may come into direct contact with the
male reproductive system. For example, certain lifestyle or occupational exposures may
lead to direct contact with MPs. Once MPs are in the testes, they might then find their
way into the semen during the process of sperm maturation and secretion and through
unknown mechanisms.
It is important to emphasize that the pathways described above are hypothetical and
require further investigation and scientific evidence to be fully confirmed. As research
progresses, it will be essential to explore the mechanisms by which MPs reach the semen
and evaluate their potential impacts on male reproductive health. It is important to keep in
mind that intrusive medical procedures might provide MPs direct access to the bloodstream
and tissues. This is a potential source of contamination. There are MPs in the air in the
operating theatre, according to recent research [85,86], which suggests that MPs may
immediately descend to the surface of patients’ viscera through air [31]. It is necessary to
look at these prospective sources’ roles more thoroughly.

4. Conclusions and Future Perspectives


The ubiquitous presence of MPs in human organs and bodily fluids has ignited signifi-
cant concerns, underscoring the need for comprehensive research and proactive measures.
This review has delved into the diverse pathways through which MPs infiltrate critical
human physiological systems, including the heart, placenta, testes, and various bodily
fluids. It has highlighted the fact that ingestion, inhalation, and dermal absorption serve
as portals for MPs’ entry, potentially having profound health implications. Furthermore,
the toxicological aspect, such as the capacity of MPs to adsorb and release toxic chemicals,
accentuates the urgency of understanding their interaction with cellular processes. How-
ever, the multifaceted challenges presented by MPs necessitate holistic risk assessments,
standardized methodologies, and public education to drive change.
Moving forward, an array of significant future directions emerge. Identifying the
sources of MPs in the environment and tracing their pathways into the human body is
crucial for developing effective strategies for prevention and reduction. Furthermore, it is
imperative to delve deeper into the mechanisms through which MPs interact with biological
systems and toxic substances, to accurately assess potential health impacts. Longitudinal
studies evaluating the chronic consequences of MPs exposure on organ function and human
health are crucial for informed decision-making. The establishment of comprehensive risk
assessment frameworks, encompassing exposure routes and toxicological interactions, will
facilitate evidence-based policies and regulations and establishing safe exposure limits.
Additionally, fostering public awareness campaigns is pivotal to incite behavioral shifts
towards responsible plastic consumption and waste management. In addressing the
intricate challenges posed by MPs’ intrusion, interdisciplinary collaborations between
environmental, medical, and policy sectors will be instrumental in safeguarding human
health and preserving the integrity of our environment.

Author Contributions: C.E.E.: Conceptualization, Methodology, Software, Formal analysis, Vali-


dation, Visualization, Investigation, Data curation, Project administration, Writing—original draft
preparation, Writing—reviewing and Editing. A.D.: Data curation, Formal analysis, Software, Visual-
ization, Writing—original draft preparation. H.K.: Resources, Writing—reviewing and Editing. Q.W.:
Resources, Funding acquisition, Writing—reviewing and Editing. M.H.R.: Writing—original draft
preparation, Writing—reviewing and Editing, Formal analysis. All authors have read and agreed to
the published version of the manuscript.
Funding: This study was partially supported by the Special Funds for Basic Research (B) (No.22H03747,
FY2022-FY2024) of Grant-in-Aid for Scientific Research of Japanese Ministry of Education, Culture,
Sports, Science and Technology (MEXT).
Environments 2023, 10, 194 15 of 18

Institutional Review Board Statement: Not Applicable.


Informed Consent Statement: Not Applicable.
Data Availability Statement: Not Applicable.
Conflicts of Interest: The authors declare no conflict of interest.

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