Microplastics: A threat to Fetoplacental unit and Reproductive systems

Abstract

Plastic pollution has become a pressing global environmental and public health challenge, raising significant concerns about its potential effects on human health. While extensive research has been conducted on micro- and nanoplastics (MNPs), there remains a critical gap in understanding how these plastic particles traverse the maternal-fetal interface and contribute to reproductive anomalies. This review aims to address this knowledge gap by examining the effects of MNPs on the fetoplacental unit, a vital structure that serves as the interface between the mother and fetus during pregnancy, as well as on the broader reproductive system. Traditionally viewed as a protective barrier safeguarding the fetus, emerging evidence suggests that the placenta may also act as a site for the accumulation of plastic particles, thereby compromising its function. A literature search was conducted using a combination of keywords on Google Scholar and PubMed including ’plastic particles affect the fetoplacental unit’, ’how plastic particles traverse the maternal-fetal contact’, and reproductive abnormalities induced by micro/nano-plastics’. Key studies show that plastic particles can traverse the maternal-fetal interface, potentially exposing developing fetuses to various harmful chemicals present in plastics, such as endocrine disruptors and persistent organic pollutants. Once in contact with the fetoplacental unit, these particles may trigger inflammatory responses, oxidative stress, and even epigenetic modifications. They also bioaccumulate in testes, altering spermatogenesis, spermatozoa morphology, testosterone production, body weights, and inflammation as reported in mice. Such disruptions can increase the risk of developmental and reproductive disorders in the fetus, suggesting that exposure to plastic particles may carry long-term health implications. Further studies highlight the particular vulnerability of the fetoplacental unit to plastic particles. The placenta has limited detoxifying capabilities and unique immunological regulation, making it especially sensitive to foreign particles. Identifying critical windows of susceptibility during pregnancy is germane, as exposure to plastic particles during these periods could have heightened effects on fetal development. This growing concern underscores the urgent need for comprehensive research into the mechanisms through which plastic particles impact the fetoplacental unit. Additionally, this review calls for stronger measures to mitigate plastic pollution and recommends health strategies aimed at protecting future generations from potential harm. It synthesizes recent findings on the ways in which these particles influence the fetoplacental unit and the broader reproductive system.

Graphical Abstract

1. Introduction

1.1. Microplastics

The term micro-nano-plastics (MNPs) describes all plastic fragments < 5 mm – which include both microplastics (MPs) and (NPs). They are distinguished by the structure and content of their polymers, which are closely related to the source of the plastic product from which they originated [98]. Polyethylene (PE), polypropylene (PP), polystyrene (PS), polyvinyl chloride (PVC), polyethylene terephthalate (PET), polycarbonate (PC), polymethacrylate (PMMA), polyisobutylene (PIB) and polyurethane (PU) are among the several polymers that make up plastics ([4], [40]). Nonetheless, the three most prevalent polymers are polyethylene, polypropylene, and polystyrene, which are present in an infinite number of cosmetics, [53], toothpaste ([75], [84], [58]), personal care and home items [30], [75]), and plastic food containers [27]. Fibres, microbeads, pieces, nurdles, and polystyrene are among the many shapes of MNPs [40].

Microplastics (MPs) are particles that are smaller than five millimeters [3], [38]. These dimensions are produced both for commercial use and by the breaking up of bigger pieces. Because MPs are seen by the host body as foreign objects inside tissues, they trigger local immune responses. Both human and marine animal intestines have been reported to contain MPs [23]. MPs are often more prevalent inside than outside [63], [90]. Therefore, all species, including humans and pregnant women, may be toxicologically affected by our indoor exposure to microplastics via dust ingestion, inhalation, or drinking water; yet, there has been little research on this subject. Indeed, it has been proposed that MPs may accumulate in humans after ingestion and result in localized toxicity by inducing and/or strengthening immunological responses, thereby impairing the body's defenses against infections and altering the use of energy reserves [91]. The placenta gently regulates the relationship between the fetus and its mother and, indirectly, the outside world via a multitude of complex systems [73]. Man-made MPs have the potential to impair this organ's sensitive capacity to discriminate between self and non-self [67]. These MPs can have several specific impacts on embryo development and can pass the umbilical cord to reach the fetus (Fig. 1).

Fig. 1.

Placenta: vulnerable unit to plastics particles’ adverse effects.

1.2. Sources and fate of microplastics and nano-plastics in the environment

Microplastics are shaped like spheres, chunks, and fibres, among other forms. Microplastics ultimately become nanoplastics as they degrade into ever-tinier garbage fragments [38], [52]. Microplastics represent an intermediate stage between larger plastic debris and nanomaterials as they degrade. Besseling et al. [7] estimate that the fragmentation of spherical microplastics might yield > 1014 times more nanoparticles. According to Phuong et al. [71], pieces, pellets, filaments and fibers, broken edges, granules, and microplastics with irregular shapes are the most common forms that microplastics assume in the environment. However, since they are used so widely in everyday life, synthetic fibers and microbeads are brought up more often. The discovery of microbeads in common cleaning, hygiene, and cosmetic products that are drained down drainage systems is comparable [15], [20]. Plastics enter the environment via a variety of routes and sources (Fig. 2; Table 1). Numerous everyday activities result in significant volumes of micro- and nanoplastics finding their way into the environment [51]. To understand the origins and ultimate destiny of microplastics and nanoplastics in the environment, we must first consider their composition and variety, which are shown in Table 1. The evaluation of small microplastics (10 µm) and nanoplastics with possible pierced cell membranes is necessary because they may have more toxicological effects than those in the gastrointestinal lumen [83]. Lab environments, where sample processing occurs, are significant sources of microplastics due to the prevalence of synthetic fibers and other plastic items indoors. It has been shown that there is a correlation between the quantity of consumer items containing polymers in the area and the additives found in samples of indoor dust [60]. Recently, increasing studies have shown that MPs were detected in food (particularly seafood) [6], sea salt, drinking water, and atmospheric fallout [16]. Due to food-chain transportation, drinks, and inhalation, plastic particles were also detected in human blood [54], human stools, colectomy specimens [45], and lungs [48]. A report has shown that the median intake of MPs (1–5000 μm) is estimated as 4.1 µg/week (or 0.58 µg/day) for an adult by correcting their actual contents in foods [64]. The daily intake of MPs with diameters between 0.5 and 10 μm is estimated as 40.1 µg/kg body weight/day from bottled mineral waters [97]. MPs accumulate in gastrointestinal tract, liver, kidney, and brain of mammals and then induce oxidative stress and inflammation response, interfere with lipid and energy metabolism, and alter blood biomarkers and neurotoxicity [95]. Collectively, these studies raise concerns about the long-term adverse effects of plastic particles on human health. Thus, due to various microplastics sources and their presence in water, soil and air, various studies have shown the presence in different organs and tissues including the placenta.

Fig. 2.

Sources and fate of micro- and nanoplastics in the environment. Micro- and nanoplastics are generated from primary and secondary sources through consumers and industries. Macroplastic products that disintegrate into micron-sized can break down into nanoplastics via biodegradation or non-biodegradation process. Both micro- and nanoplastics can occur in both aquatic and terrestrial environments, and eventually enter the food chain and water supplies, leading to the uptake and bioaccumulation of these plastic particles in the human body including pregnant women.

Table 1.

Sources and Fate of Microplastics and Nanoplastics in the Environment.

	Examples/Produces	Quantity	References
Pathways	Washing clothing made of synthetic fibers like acrylic, fleece, and polyester	50 % of the one million tons of synthetic fibers that enter wastewater streams each year and go into the environment	[51]; [87]
	Exfoliants and toothpaste	There may be up to 4000 microbeads per 1.6 g (the typical amount of toothpaste applied).	[13]
	Tire dust, such as that utilized for road markings and home exteriors, is produced because of tire deterioration.	Produce more than 1400 mg of microplastics per kilometer and paint. 10 % of the microplastic pollution entering the environment	[31]; [86]; [51]
Sources	Categories	Examples	References
	Primary	Engineered as industrial abrasives, microbeads in exfoliants and other hygiene and cosmetic items, pellets for making larger plastic products, and emissions from 3D printers	[20]; [15]; [82]
	Secondary	Typically observed in the environment because of UV exposure and physical abrasion.	[47]
Means of Contamination	Direct	when plastic is applied or utilized on purpose, such as in mulch, greenhouse building materials, and soil conditioners.	[68]; [8]
	Indirect	by sludge land applications and irrigation using treated or untreated municipal and industrial wastewater.	[25]; [2]

1.3. Fetoplacental Unit

The fetus, placenta, and mother make up the interdependent fetoplacental unit, sometimes referred to as the feto-placento-maternal unit. The necessary elements are given to the fetus to engage in the complex regulatory process that establishes the exchange and interplay between the endocrine and physiological systems of the mother and the fetus (Fig. 2). There are two distinct circulatory systems in the placenta. Every circulatory system has a blood pool where the mother and the fetus exchange gases, nutrition, and waste products. This is accomplished by the anemic blood leaving the fetus's umbilical arteries and traveling via the chorionic villi to the placenta, where it gets all the nutrition and oxygen it needs. After passing through capillaries to pick up nutrients and discard waste, oxygenated blood travels back via the umbilical vein to the fetus. The mother's blood experiences an oxygen deficit, which is subsequently expelled from the mother's veins via the maternal veins. Three weeks after conception, blood from the fetus travels via veins rather than arteries (and blood with low oxygen content through arteries instead of veins). The newborn circulatory system operates after birth. As per the findings of [69], the fetoplacental unit performs three crucial functions: (i) providing the mother's circulation with protein and steroid hormones; (ii) acting as a barrier that restricts communication and interaction between the fetal and maternal endocrinological and physiological systems; and (iii) participating in the regulation of parturition, endocrine function, and fetal growth and development.

In addition, fetoplacental unit helps in the following

i. Transport of gases, nutrients, and waste occurs via the endometrium's spiral arteries.

ii. Oxygenated blood is delivered through maternal arteries to the fetal pools.

iii. The fetus exchanges waste products via the umbilical arteries

It should be noted that, oxygen-depleted blood leaves the mother's blood pool via the veins. During pregnancy, veins carry oxygenated blood to the fetus, but after birth, this function is reversed [69].

1.4. Impact of MNPs on the fetoplacental unit

Numerous in vitro, animal, and human ex vivo investigations show that MNPs' absorption by placental cells is facilitated by their smaller size and higher concentration ([14], [26]; [81]; [37]; [35]; [89]). Both maternal mice and rats exposed to PS-NPs during pregnancy showed evidence of these particles in the fetal liver (96, [14]), heart [14], brain ([14]; [93]), lung ([14], [32]), and kidney [14]. The particles ranged in size from 20 to 500 nm. Remarkably, a comparable exposure with PE-MPs (10–45μm) only caused MP accumulation in the fetal kidneys [37]. In animals and a few In vitro studies, microplastic exposure has been shown to disrupt fetal-maternal exchange by interfering with critical processes in the placenta. Microplastics, often carrying toxic chemicals or acting as carriers for pollutants, can cross biological barriers and accumulate in placental tissue [32], [35]. This accumulation may lead to:

• 1.Inflammation and Oxidative Stress: Microplastics can trigger inflammatory responses or oxidative stress in placental cells, which may impair nutrient and oxygen transfer to the fetus.
• 2.Hormonal Disruption: Chemicals associated with microplastics, such as endocrine-disrupting compounds, can interfere with hormone signaling essential for maintaining pregnancy and supporting fetal growth.
• 3.Physical Barrier Disruption: The presence of microplastics in the placenta may obstruct cellular pathways or directly damage placental structures, reducing efficiency in transferring nutrients, gases, and waste products between mother and fetus.

Although the implications of plastic pollution on health are becoming more understood, little is known about how it affects the fetoplacental unit and reproductive systems. Therefore, to comprehensively review the impact of micro- and nanoplastics (MNPs) on the fetoplacental unit, focusing on their absorption and transference across the placenta, accumulation in fetal organs, and the potential consequences for fetal development and reproductive health, this review synthesized findings from in vitro, animal, and human ex vivo studies to understand the mechanisms and implications of MNP exposure during pregnancy.

Humans may inject microplastics directly (via consumption of microplastic-contaminated water, soil or salt) or indirectly via trophic transfer (e.g. via consumption of microplastic-contaminated seafood and plant) or inhaling airborne microplastics. The greatest exposure might be through seafood consumption, serving as a major protein source and as the sea happens to be a hot spot for plastic debris pollution. Food and Agricultural Organization in their 2016 report on “the state of the world fisheries and aquaculture” reported that in 2015 alone, 6.7 % of human protein and 17 % of animal protein consumed globally were from seafood [28]. Microplastics can determine gamete abnormalities. MPs cannot penetrate the embryo, but by covering the surface of the chorion, they prevent oxygen uptake, with serious consequences for embryo health and hatching. In addition, this review introduces a novel perspective by examining the fetoplacental unit as a direct target for micro- and nanoplastic accumulation rather than solely as a protective barrier during pregnancy. It synthesizes emerging evidence that plastic particles can traverse the maternal-fetal interface, potentially disrupting placental function and fetal development. This review aims to address this knowledge gap by examining the effects of MNPs on the fetoplacental unit, a vital structure that serves as the interface between the mother and fetus during pregnancy, as well as on the broader reproductive system.

2. Materials and Methods

The literature search for this review was performed comprehensively on Google Scholar and PubMed databases to identify relevant studies examining the impact of plastic particles on the fetoplacental unit, as well as associated reproductive implications. A combination of specific keywords was employed to retrieve relevant research, including terms such as “plastic particles affect the fetoplacental unit,” “how plastic particles traverse the maternal-fetal contact,” “microplastics implications on the reproductive system and fertility,” and “reproductive abnormalities induced by micro/nano-plastics (MNPs).” The search aimed to cover a wide array of studies that explore both the physiological interactions of plastic particles with the fetoplacental unit and potential long-term impacts on fetal health and reproductive outcomes.

Inclusion Criteria:

• 1.Study Focus: Only studies that specifically investigate the effects of microplastics or nanoplastics (MNPs) on the fetoplacental unit or reproductive system were included.
• 2.Study Type: Original research articles, systematic reviews, and meta-analyses were considered, with a focus on human, in vivo animal models, and in vitro studies.
• 3.Publication Date: Studies published within the past 20 years were prioritized to ensure the most recent data and emerging trends in the field were included.
• 4.Language: Only studies published in English were included to maintain consistency in data interpretation.
• 5.Data Quality: Studies were evaluated for methodological rigor, specifically looking for well-documented methodologies, sample size appropriateness, and robust statistical analysis.

Exclusion Criteria:

• 1.Non-Relevant Topics: Articles that discussed plastics broadly without addressing their effects on the fetoplacental unit or reproductive health were excluded.
• 2.Non-Peer-Reviewed Sources: Studies lacking peer review, including conference abstracts, opinion pieces, and popular science articles, were not included to ensure high-quality data.
• 3.Redundant Studies: Duplicate studies or studies with overlapping data were removed to maintain a unique and non-redundant dataset.
• 4.Insufficient Data: Studies with incomplete information on experimental design, outcomes, or lacking statistical validation were excluded to ensure the robustness of the review’s findings.

3. Results and Discussion

Plastic pollution has become a significant environmental and public health concern, as highlighted by recent studies which underscore its widespread environmental presence and potential risks to human health, with microplastics and nanoplastics posing particular risks to human health. Recent studies have begun to elucidate the impact of these particles on the fetoplacental unit, an essential interface between mother and fetus during pregnancy. Traditionally viewed as a protective barrier, the placenta is now recognized as a vulnerable target for accumulating plastic particles, with potential long-term implications for fetal development and health. Microplastics may harm various organs, including the neurological, digestive, reproductive, and developmental systems, and can interfere with an organism's capacity to function appropriately [94]. Different model systems including rats, mice, zebrafish among others have been used to evaluate reproductive toxicity of MNPs and their impacts on the fetoplacental unit (Table 2). Hou et al. [42] reported that exposure to PS-NPs reduced the epididymis' live sperm to total sperm, causing two-tailed, hookless, or larger neck spermatozoa (Table 2). Jin et al. [49] also showed MPs bioaccumulation of MPs in mouse testes, altering spermatogenesis and morphology (Table 2). Workers in the plastics sector have reported problems with infertility in women and low sperm quality in males [44]. In fact, plastic micro- and nanoparticles may pose a greater threat to the reproductive system. Many animal tests have been conducted in an attempt to understand the effect of MPs on male and female fertility [36]. Reproductive toxicity is defined as exposure to any drug that interferes with the normal function of the female and male reproductive organs and causes a loss of fertility, according to the United Nations Economic Commission for Europe (UNECE., 2011). Chronic exposure to toxins and pollutants in the environment, such as MPs, may affect both male and female fertility [88]. MPs may also cause sperm to lose their acrosomes, have a small or non-existent head, and experience other morphological changes [49]. MNPs may have detrimental effects on various organs and functions, including reproductive ones, and can worsen when combined with other dangerous chemical xenobiotics. According to Fred-Ahmadu et al. [33], MPs and NPs may operate as vectors for other pollutants, enabling their biomagnification.

Table 2.

Effects of MNPs on the reproductive system and/or their crosslink to the placenta.

Model systems	Type of MPs	Size	Concentration	Exposure time	Findings	References
Male Mice	PS	5 µm	100 µg/L, 1000 µg/L, and 10 mg/L	35–75 days	Exposure reduced the proportion of living sperm in the epididymis relative to total sperm, leading to physically abnormal spermatozoa, including two-tailed forms, hookless shapes, and enlarged necks. Morphological examination of the testis germinal epithelium revealed significant cellular damage, characterized by reduced spermatid numbers, cell detachment, pyknosis, and nuclear rupture. Additionally, inflammatory gene expression was elevated (NF-κB p65, p-NF-κB p65, IL−1β, IL−6, and TNF), while transcriptional factors and downstream targets of the antioxidant defense system (Nrf2 and HO−1 proteins) were diminished. The Bax-to-Bcl2 ratio was increased, indicating enhanced apoptosis.	[42]
Mice	PS	(0.5, 4, 10 μm)	(100 μL PS-MPs (10 mg/ml))	28 days	MPs bioaccumulate in mouse testes, altering spermatogenesis, spermatozoa morphology, testosterone production, body weights, and inflammation. MPs enter germ, Sertoli, and Leydig cells in vitro.	[49]
Female Wistar rats	PS	0.5 μm	0.015–0/15 mg/kg/d group	90 days	HE staining revealed fewer developing follicles in the exposed group compared to controls. Antioxidant enzyme activities (GSH-Px, CAT, SOD) were reduced, while MDA levels increased in ovarian tissue. Immunohistochemistry showed elevated NLRP3 and Cleaved-Caspase−1 densities in granulosa cells (13.9 % and 14 % higher in the 1.5 mg/kg/d group). ELISA results indicated lower AMH levels (by 23.3 pg/ml) and higher IL−1β (32 pg/ml) and IL−18 (18.5 pg/ml) levels. TUNEL staining and flow cytometry confirmed increased granulosa cell death. Western blot analysis revealed activation of the NLRP3/Caspase−1 pathway and increased Cleaved-Caspase−3, suggesting PS MPs induce pyroptosis and apoptosis in granulosa cells via this signaling pathway.	[43]
Male rats	PS-NPs	38.92 nm	1, 3, 6 and 10 mg/kg-day	5 weeks	PS NP exposure showed significant negative correlations with serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels. Tissue and cellular impairments were observed even at the lowest dose, with lesion severity increasing dose-dependently. DNA damage, altered sperm morphology, and reduced viability were dose-related. Downregulation of PLZF, DAZL, FSH, and LH gene expressions in the testis indicated disruption of spermatogenesis and the HPT axis, as confirmed by physio-histological changes and fluorescence imaging. Interestingly, FSH and LH expressions were elevated at the highest dose, revealing a nonlinear dose-response. ABP modulation also showed a nonlinear pattern, while GnRH levels unexpectedly increased, with reduced sensitivity at higher doses.	[1]
Sprague Dawley rats	PS-NPs	20 nm	900 μL	180 min	The mother had nanopolystyrene in her lungs, heart, and spleen. Polystyrene nanoparticles were in the placenta. Because maternal pulmonary exposure to nanopolystyrene translocates plastic particles to placental and fetal cells, the fetoplacental unit is vulnerable to harm.	[32]
Male mice	PS	5.0–5.9 μm	0.01–1 mg/d	6 weeks	ROS and JNK/p38 mitogen-activated protein kinases produced a substantial drop in sperm quantity and motility, an increase in sperm deformities, and a decrease in testosterone (p38-MAPK). SDH and LDH activities also influenced sperm metabolism, which was surprising.	[92]
Mice	PS	0.5 and 5 μm	100 and 1000 μg /L		The F1 offspring had altered serum triglyceride (TG), total cholesterol (TC), HDL-C, and LDL-C levels, as well as hepatic TC and TG. The 5 μm MPs-treated groups are more likely to have metabolic problems in their kids due to maternal exposure.	[56]
Zebrafish	PS	1 μm	(10, 100, and 1000 μg/L)	21 days	Increased apoptosis levels in male testes at 1000 μg/L were observed, leading to increased p53-mediated apoptotic pathways and a significant reduction in testis basement membrane thickness.	[77]
Zebrafish	PS-NPs	42 nm	90, 45, and 120 mg/ml		Co-parental PS NP exposure had no significant effect on reproductive success. In F0 fish, PS NPs reduced glutathione reductase activity in the brain, muscle, and testes but did not impact heart or gonadal mitochondrial function. PS NPs were detected in the yolk sac, gastrointestinal tract, liver, and pancreas of maternally and co-parentally exposed F1 embryos and larvae. Additionally, these embryos exhibited bradycardia, along with reduced glutathione reductase activity and thiol levels following maternal and/or co-parental exposure.	[72]
ex vivo human placental perfusion	PS-NPs	> 87 nm	-	-	Placental PS-NPs and artifacts were found. To eliminate artifacts in placental translocation studies utilizing fluorescent PS beads, NP size distribution, modification, and fluorescent dye leakage should be examined physiologically.	[34]
ex vivo human placental perfusion	PS-NPs	50–300 nm	-	-	Fetal-to-maternal polystyrene particle transfer was far greater than maternal-to-fetal. The placental syncytiotrophoblast aggregated all polystyrene particles independent of their capacity to cross the placental barrier or perfusion direction.	[34]
Advanced in vitro co-culture	PS	50 nm and 0.5 μm			No considerable transportation of PS through the intestinal and placental barriers, but there was intercellular distribution.	[39]
ex vivo human placental perfusion	PS-NPs	80 nm	-	-	PS transport over the barrier was investigated by quantitative and qualitative plasma protein changes. After the PS-proteome analysis, human albumin and immunoglobulin G were tested to determine whether they may explain enhanced placental PS-transfer. In contrast to the IgG-corona, the protein corona created by human albumin significantly increased PS-particle transmission throughout tissue.	[35]
Human	12 MPs	5–10 μm	-	-	In four human placentas, 12 microplastic fragments were discovered: five on the fetal side, four on the maternal side, and three on the chorioamniotic membranes.	[78]
Human	-	> 50μm	-	-	Human placenta and meconium samples included polyethylene, polypropylene, polystyrene, and polyurethane, although only the latter was airborne in the operating area, suggesting contamination.	[10]

PS: Polystyrene;

MNPs (70nm-45µm) have been shown to originate in the gut and are absorbed prior to reaching other organs, such as the gonads [80], [94]. However, the blood-gonad barrier only permits the accumulation of tiny NPs and may block the entry of bigger MPs [80]. Furthermore, many reproductive organs, including the human placenta, may accumulate NPs (240 nm) [78]. This may alter the functioning of the reproductive organ (i.e., ovarian issues, spermatogenesis issues, and sperm quality issues) [1].

Long-term MP exposure thereby exacerbates a number of toxicities, such as reduced ovarian reserve, shrunken or empty follicles, inflammatory ovaries, and decreased oocyte diameter and quantity [55]. It is difficult to evaluate MPs' harmful impact on people. More research with a mechanistic emphasis is needed to completely understand the detrimental effects of MPs on both male and female reproductive systems. The toxicity of MPs linked with reproduction is not well understood now.

The placenta is one of the most important organs for life support throughout pregnancy [5]. It is hemochorial, meaning that the fetal chorion and mother blood come into direct contact, and it has a discoid form that is unique to non-human primates, rabbits, and rodents [5]. Grafmueller et al. [34] investigated the transport mechanisms behind the placental transfer of PS-NPs (50–300 nm) using the ex vivo human placenta fusion model (HPFM) (Table 2). Furthermore, 240 nm PS may pass through the placental barrier, according to a model of the perfusion of the human placenta [89]. Studies revealed that PS-NPs were collected in the syncytiotrophoblast tissue of the placenta. Thus, the flow of PS-NPs into the human placenta is regulated by the syncytiotrophoblast. Ex vivo placenta perfusion models have been used in recent studies to demonstrate the mobility of nanoplastic particles (100 nm) around the placenta and their correlation with alterations in the corona's protein composition [35], [6] (Table 2). The cellular absorption and intracellular accumulation of nano- and microparticles have also been shown in vitro co-culture models of the placenta [39]. In conclusion, a fairly recent study discovered that MPs sized between 5 and 10 µm were present in 5 out of the placentas delivered vaginally [78] (Table 3). The question of whether MP actually accumulates in the placenta during pregnancy is crucial because microparticles can alter multiple cellular regulatory pathways in the placenta, which can affect both placental and fetal development [46]. Twelve microplastic particles, with sizes ranging from 5 to 10 µm, were discovered in four out of six placentas delivered vaginally, according to recent research. The most common substance, according to their findings, was polypropylene [78] (Table 2). Human organs have previously been shown to contain these minuscule foreign particles [85]; nevertheless, the mechanism by which these particles are swallowed remains unclear. Given the placenta's critical role in fetal development and its function as a conduit between the fetus and its environment, exogenous and possibly dangerous MP particles are a major issue [78].

Table 3.

Detection of MPs/NPs in human placenta.

Species	MNPs Type	MNPs Size	MNPs Shape	Exposure Time	Effects	Reference
Human Placenta	MPs	Varies	Beads, irregular shape	-	MPs fragments are found in the tissues of the human placenta.	[78]
	PS	0.5, 50 nm	Beads	24 h	PS particle internalization in placental cells.	[89]
	PS	50, 80, 240, 500 nm	Beads	3 h	PS particles' ability to cross the placental barrier in a size-dependent way.	[39]

Numerous studies have reported evidence of microplastics translocating across the placenta and accumulating in fetal tissues. For instance, Gruber et al. [35] and [14]) demonstrated MNP presence in fetal organs such as the liver, brain, and lungs, attributed to their small size and high concentration. In contrast, other studies, such as Wick et al. [89], found limited evidence of translocation under certain experimental conditions, potentially due to differences in particle properties (e.g., size, charge, and chemical composition) and biological variability among species. Our findings corroborate the view that particle size, concentration, and the unique immunological environment of the placenta are key determinants of MNP translocation. These discrepancies underscore the need for standardized methodologies in studying MNP behavior across different biological models.

According to PrabhuDas et al. [73], the placenta serves as a vital interface by preserving the link between the fetus and the outside world as well as the fetal environment and the mother environment. According to Nancy et al. [67], microplastics may negatively impact an embryo's capacity to differentiate between itself and non-self, hence impairing the unique response system. According to [78], microplastic pieces were discovered for the first time by a very sensitive spectroscopy (Raman Microspectroscopy) in the human placenta samples of six (consenting) patients who had uncomplicated pregnancies. This investigation turned up twelve distinct types of microplastic pieces. Twelve pieces of microplastic, ranging in size from 5 to 10 m and shaped spherically or irregularly, were found in four placentas: four on the maternal side, three in the chorioamniotic membranes, and five on the fetal side (Table 2 and Table 3). Each microplastic particle was identified by its morphological and chemical characteristics. Nine of them could only be recognized by their colors and were all used in manufactured goods. Three of them (mostly a thermoplastic polymer) were identified as stained polypropylene.

Emerging evidence suggests that plastic particles can traverse the maternal-fetal interface, as demonstrated by studies such as Ragusa et al. [78], which identified microplastics in human placental tissue, and Braun et al. [11], who reported evidence of plastic particle translocation across the placental barrier. exposing the developing fetus to harmful chemicals contained within plastics, such as endocrine disruptors and persistent organic pollutants (POPs). These chemicals are of particular concern because of their ability to disrupt hormonal regulation and normal fetal development. For instance, endocrine disruptors are known to interfere with the endocrine system, leading to developmental and reproductive abnormalities. The ability of plastic particles to penetrate the placental barrier highlights the inadequacy of this organ to fully shield the fetus from foreign materials, which can result in unanticipated risks.

Once in contact with the fetoplacental unit, microplastics and nanoplastics can initiate a cascade of adverse biological effects. Studies by Prata et al. [74] and Hou et al. [43] have demonstrated that microplastics can trigger inflammatory responses and oxidative stress, primarily through the overproduction of reactive oxygen species (ROS) and subsequent cellular damage. Inflammatory responses and oxidative stress are among the primary mechanisms identified in recent studies. Oxidative stress results from an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, which can cause cellular damage and disrupt normal placental function. Such disruptions are particularly concerning given the critical role of the placenta in nutrient exchange and fetal growth.

Furthermore, plastic particle exposure has been shown to induce epigenetic modifications—heritable changes in gene expression. For example, research by Campanale et al. [12] and Luo et al. [57] demonstrated that microplastic exposure can alter DNA methylation patterns and histone modifications, leading to disruptions in normal fetal development. changes in gene expression without altering the DNA sequence. Epigenetic changes can have lasting impacts on fetal development, increasing the risk of long-term health issues such as developmental and reproductive disorders. These findings emphasize the particular sensitivity of the fetoplacental unit to environmental stressors, such as plastic particles, during critical windows of pregnancy.

The placenta's limited detoxification capabilities and its unique immunological regulation make it particularly vulnerable to plastic particles. Studies such as Ragusa et al. [78] and Braun et al. [11] highlight the placenta's inability to fully filter out foreign materials, including microplastics, which can impair its function and increase fetal exposure to harmful substances. make it especially susceptible to the accumulation and adverse effects of plastic particles. Unlike other organs, the placenta's immune environment must balance tolerance to the fetus while maintaining defense against harmful agents. This delicate balance may be disrupted by the presence of foreign plastic particles, exacerbating inflammatory responses and impairing placental function.

Identifying critical windows of susceptibility during pregnancy is crucial, as exposure during these periods may have heightened effects on fetal development. For example, early pregnancy represents a phase of rapid cellular division and organogenesis, during which the fetus may be particularly vulnerable to the toxic effects of microplastics and nanoplastics. Understanding these critical periods will help to develop targeted strategies for reducing exposure and mitigating potential harm.

Despite extensive sanitation measures, humans face a growing risk of exposure to MNP particles via inhalation or ingestion but also via inhalation, as these particles are increasingly present in the air [59]. Chronic exposure to MNPs has been shown to induce elevated production of reactive oxygen species (ROS), leading to increased oxidative stress [22], [50]. Oxidative stress is closely linked to cellular senescence, a state characterized by considerable cellular damage and arrest [29], which contributes to a heightened vulnerability to carcinogens [70], immune system decline [18], and cognitive deterioration [41], [66], [96]. Prolonged oxidative stress in human cells has been associated with inflammation, and respiratory diseases [24], [65], [9]. Studies also show an increase in inflammatory markers in cells exposed to MNPs ([76]; Hu et al., 2020). This persistent inflammation can disrupt the cell cycle, ultimately triggering cellular senescence [79].

Given the compelling evidence that the fetoplacental unit is vulnerable or sensitive to MPs, the fetus may be susceptible to neurodevelopmental alterations that might ultimately affect behavioural performance [78]. Disruptions may result from a variety of factors. Changes in neurotransmitter activity at a key developmental stage, such as being exposed to MP while pregnant, may cause long-term deficits in behavior and cognition. MPs, such as Polystyrene nanoplastics (NPs), have also been shown to hinder reproduction and cause aberrant embryonic development in the freshwater crab Daphnia galeata [19]. Due to the epigenetic change of key genes in stress response systems, fetal programming of MPs during pregnancy may have long-term effects on neurobehavioral development. A recent study suggests that MPs might be harmful to men's ability to conceive [21]. Interestingly, it's been shown that altering the epigenetic profile of gametes may have long-term effects, increase a child's vulnerability to disease, premature embryo development, and poor fertilization [17], [61]. This review implies that the identification or detection of microplastics in animals or human placental tissues highlights potential risks of bioaccumulation in fetal tissue, contributing to growing concerns about their impact on development. These implications include:

• 1.Evidence of Maternal-Fetal Transfer: Microplastics presence in the placenta suggests that these particles could cross placental barriers, potentially reaching the fetus and accumulating in fetal tissues.
• 2.Chemical Load Transfer: Microplastics often carry toxic substances, such as heavy metals or endocrine-disrupting chemicals. Their presence in the placenta raises concerns about these harmful compounds being transferred and accumulating in fetal systems.
• 3.Impairment of Placental Function: Microplastics in placental tissues may disrupt nutrient and oxygen exchange, potentially compromising fetal growth and increasing the risk of developmental abnormalities.
• 4.Long-Term Bioaccumulation Risks: If microplastics can persist and bioaccumulate in the fetus, they might pose long-term health risks, including chronic inflammation, oxidative stress, and impacts on organ development.

Emerging evidence suggests different potential mechanisms for MNP translocation revealing that the placental barrier is not impermeable to exogenous particles such as MNPs. Studies have shown that nanoplastics can be internalized via receptor-mediated endocytosis, leveraging placental cells’ physiological role in nutrient uptake. A recent study by Dusza et al. [26] showed that size-dependent placental uptake of pristine and weathered MNPs (PS; 0.05 −10μm) was observed in different placental cell types after 24 h exposure. The uptake is influenced by particle size and surface chemistry, with smaller and more hydrophilic particles exhibiting higher translocation rates. MNP exposure can induce oxidative stress and inflammation in placental cells [32], disrupting tight junctions and facilitating particle movement across the barrier. Endocrine-disrupting chemicals often associated with microplastics may impair placental function by interfering with hormone signaling critical for maintaining pregnancy [35]. This disruption could exacerbate permeability and nutrient transport inefficiency. Accumulated MNPs may physically obstruct cellular pathways or damage structural components of the placenta, further compromising its barrier function.

Therefore, MNPs in general can potentially disrupt numerous cellular regulatory pathways within the placenta, significantly impacting its ability to maintain a healthy pregnancy environment. These particles may interfere with key immune mechanisms essential for maintaining maternal-fetal tolerance during pregnancy, potentially leading to an imbalance in the immune response. MPs may also impair growth-factor signaling pathways that are critical during and after embryo implantation, thereby affecting the proper establishment of the placenta [78].

Additionally, MPs may compromise the functions of atypical chemokine receptors, which play a vital role in maternal-fetal communication, as well as disrupt critical signaling pathways between the embryo and the uterine environment that are necessary for fetal development. MPs may also interfere with the trafficking of uterine dendritic cells, natural killer cells, T cells, and macrophages—immune cells that are vital for a normal pregnancy. These immune cells facilitate maternal-fetal interactions, promote proper vascular remodeling, and protect against infections, ensuring the development of the fetus in a stable and safe environment.

The cumulative effects of these disruptions can lead to adverse pregnancy outcomes, including preeclampsia—a condition characterized by high blood pressure and damage to organ systems—and fetal growth restriction, which can severely affect the health and development of the fetus [46] (Fig. 3). Therefore, several studies confirm the placental translocation of MNPs depends on their physicochemical properties such as size, charge, protein corona formation and chemical modification [62].

Fig. 3.

Potential mechanisms by which microplastics traverse the maternal-fetal interface.

Mechanistic insights reveal several pathways facilitating MNP traversal via endocytosis and cellular uptake, oxidative stress and inflammation, hormonal disruption or physical damage into the fetoplacental unit.

h: hours; MPs: microplastics; PS: polystyrene; u: unknown

4. Summary

• 1.The fetoplacental unit, traditionally seen as a barrier protecting the fetus, may be compromised by exposure to plastic particles. Micro- and nanoplastics can traverse the maternal-fetal interface, potentially exposing developing fetuses to harmful chemicals associated with plastics, including endocrine disruptors and persistent organic pollutants.
• 2.The presence of plastic particles in the fetoplacental unit can induce inflammatory responses, oxidative stress, and even epigenetic changes. These disruptions increase the risk of developmental and reproductive disorders, suggesting that exposure to plastic particles may have long-lasting health consequences for the fetus.

5. Conclusion

This review investigates the mechanisms and pathways through which micro- and nanoplastics (MNPs) cross the maternal-fetal interface, shedding light on their impact on placental functionality and fetal development. The accumulation of these particles in the placental environment has been shown to induce inflammatory responses, oxidative stress, and epigenetic modifications. They also bioaccumulate in testes, altering spermatogenesis, spermatozoa morphology, testosterone production, body weights, and inflammation as reported in mice. The vulnerability of the fetoplacental unit, compounded by its limited detoxification capacity and unique immunological regulation, underscores the need to identify critical windows of susceptibility during pregnancy. By integrating findings with existing studies on microplastic toxicity and critically analyzing contrasting perspectives, this study provides a deeper understanding of the intricate processes involved. Comprehensive research into the mechanisms of particle transfer and their biological impacts on reproductive health remains critical to fully understand and address these risks.

6. Limitations

The following are the limitations of this review;

• 1.The precise pathways through which MNPs transverse into biological barriers, including the maternal-fetal interface, especially in humans, remain unclear.
• 2.Most studies are based on animal models or in vitro experiments, with limited direct evidence from human populations, particularly pregnant women.

7. Recommendation and Future Directions

Due to its limited detoxification abilities and unique immunological environment, the placenta is particularly sensitive to foreign particles like MNPs. Therefore, there is an urgent need for comprehensive research into the mechanisms of plastic particle impact on the fetoplacental unit in humans, along with policy measures to mitigate plastic pollution. Protecting future generations from potential harm will require targeted health strategies and a deeper understanding of how plastic pollution intersects with reproductive health.

CRediT authorship contribution statement

Anifowoshe Abass Toba: Writing – original draft, Software, Data curation, Conceptualization. Akhtar Md Noor: Writing – review & editing, Data curation. Nongthomba Upendra: Writing – review & editing, Conceptualization. Singh Asem Sanjit: Writing – review & editing, Data curation. Ismail Toyyibah Funmilayo: Writing – review & editing, Formal analysis. Majeed Abisola: Writing – original draft, Investigation, Formal analysis.

Declaration of generative AI and AI-assisted technologies in the writing process

During the preparation of this work, the author(s) used ChatGPT to improve language. After using this service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Handling Editor: Prof. L.H. Lash

Data Availability

Data will be made available on request.