Health Risks of Prenatal and Early-Life Microplastics Exposure: A Comprehensive Review

Abstract

Microplastics (MPs) and nanoplastics (NPs) are emerging environmental contaminants that have raised increasing concern regarding their potential health effects. During pregnancy and early life, developing organisms are particularly vulnerable due to immature biological barriers and the dynamic nature of organogenesis. This review summarizes current evidence on maternal and early life exposure routes to MPs and NPs, including oral ingestion, inhalation, dermal contact, and transplacental transfer. Laboratory and epidemiological studies have demonstrated that microplastics can cross the placental barrier, potentially impairing placental function, altering fetal growth, and compromising pregnancy outcomes. Experimental data from animal models and in vitro systems suggest that maternal MP exposure may contribute to adverse neonatal development via multiple mechanisms including oxidative stress, inflammation, endocrine disruption, and epigenetic alterations. These toxicological pathways have been implicated in neurodevelopmental abnormalities, reproductive dysfunction, and immune dysregulation, often in a sex-dependent manner. Despite increasing experimental evidence, major knowledge gaps remain regarding human exposure levels, dose–response relationships, and long-term health implications. Future research should focus on improving detection sensitivity, establishing standardized exposure models, and developing targeted risk assessment frameworks to evaluate microplastic-associated health risks during pregnancy and early development.

1. Introduction

Microplastics are considered one of the most concerning emerging pollutants in the fields of environment and health. The global production of plastics has increased exponentially over the past five decades, rising from modest levels in 1964 to 311 million tonnes by 2014, a 20-fold increase. This trend is expected to continue, with projections indicating production will reach 622 million tonnes by 2034 and potentially double again by 2050. Alongside this rapid growth, plastic debris has accumulated extensively across marine, terrestrial, and atmospheric environments. Due to environmental factors such as mechanical abrasion, ultraviolet radiation, temperature fluctuations, and humidity, larger plastic waste degrades into smaller fragments collectively known as microplastics. Microplastics originate from a wide range of sources. Primary microplastics are manufactured intentionally, such as those used in personal care products or released from synthetic textiles. In contrast, secondary microplastics are generated unintentionally through the degradation of mismanaged plastic waste via photodegradation, abrasion, and microbial activity. Sources of microplastics include industrial emissions, waste incineration, traffic-related wear, synthetic fabrics, consumer products such as masks and cutting boards, and other anthropogenic activities. , As a result, microplastics have become a pervasive environmental contaminant, with their presence documented in remote areas ranging from Antarctica to Mount Everest. The discovery of microplastics in the human body has shifted public concern from environmental pollution to potential health risks. Microplastics have been detected in various biological matrices, including faeces, alveoli, placenta, sputum, and even the bloodstream. − At the same time, it was also found that microplastic exposure can lead to a variety of toxic outcomes, including gastrointestinal damage, liver toxicity, lung toxicity, and damage to the nervous system.

The first 1,000 days of lifedefined by the World Health Organization (WHO) and the United Nations Children’s Fund (UNICEF) as the period from conception to a child’s second birthdayrepresent a critical window for development, during which tissues, organs, and physiological systems undergo rapid and sensitive maturation. During this vulnerable period, the human body is particularly susceptible to environmental insults. Exposure to toxicants during early life has been linked to adverse outcomes including impaired physical and neurological development, altered metabolism, immune dysfunction, reproductive abnormalities, and an increased risk of chronic diseases in adulthood. , Recent data have raised particular concerns about microplastic exposure during this sensitive developmental window. A large-scale analysis of over 9,000 placental samples revealed a dramatic rise in the detection rate of microplastics from 60% in 2016 to 100% by 2021, highlighting the growing likelihood of prenatal exposure. These findings underscore the urgent need to understand the potential hazards of early life exposure to microplastics and to elucidate the underlying biological mechanisms. Such knowledge is essential to support accurate health risk assessment, establish science-based safety thresholds, and inform the development of regulatory policies aimed at mitigating microplastic contamination.

This review summarizes the existing evidence on microplastic exposure and its transplacental transport and evaluates its potential impact on pregnancy outcomes, focusing on the different risks faced by mothers and offspring during pregnancy exposure and their potential mechanistic pathways. Through a comprehensive summary and analysis, it aims to deepen the understanding of the health risks associated with early microplastic exposure, provide a basis for more researchers to conduct research on microplastic toxicity and health risks, and remind researchers to pay attention to the adverse outcomes of parental exposure on offspring.

2. Pathways and Biological Evidence of Prenatal and Early-Life Microplastics Exposure

Understanding the exposure pathways and internal distribution of microplastics during pregnancy and early life is critical for assessing internal exposure levels and associated health risks. Owing to their small particle size, microplastics can traverse biological barriers, including the placental barrier, raising particular concern during fetal developmenta period of heightened vulnerability to environmental insults. Emerging evidence suggests that microplastics can accumulate in both maternal and fetal tissues, potentially disrupting essential developmental processes. This section provides an overview of the major sources and exposure routes of microplastics during the prenatal and early postnatal stages and summarizes current research on their biodistribution and ability to cross the placental barrier (Figure ).

1.

Visualization of exposure pathways and transplacental transfer. Microplastics may enter the human body through ingestion, inhalation, and dermal contact and then reach the placenta via the bloodstream or the vaginal–uterine pathway, and further transfer to the fetus, posing potential health risks.

2.1. Microplastics Exposure during Pregnancy

Oral ingestion is widely recognized as the primary route of microplastic exposure in pregnant individuals, with a broader range of sources compared to other pathways. It is estimated that the average person ingests between 39,000 to 52,000 microplastic particles annually. While early studies emphasized seafood products such as oysters, − mussels, and fish , as key contributors due to trophic transfer and bioaccumulation, recent evidence suggests that commonly consumed food items may represent more significant sources. These include table salt, , honey, bottled water, , and take-out containers. For pregnant individuals, exposure from daily use items raises a particular concern. For example, microwaving plastic food containers for just 3 min can release up to 4.22 million microplastic particles and 2.11 billion nanoplastic particles per square centimeter of plastic surface. Similarly, disposable paper cups lined with plastic can leach approximately 25,000 microplastic particles into 100 mL of hot water after 15 min of contact. Plastic cutting boards also represent a non-negligible exposure source, with estimated annual intake ranging from 7.4 to 50 g per person. Following ingestion, microplastics may initially accumulate in the tonsils, while unretained particles continue into the gastrointestinal tract. Among gastrointestinal segments, the colon appears to harbor a higher diversity and abundance of microplastics compared with the stomach and small intestine. Particles smaller than 5 μm can cross the intestinal epithelium, entering the lymphatic system and systemic circulation. ,, Meanwhile, larger particles (5–10 μm) may be retained in Pyle collecting lymph nodes, potentially disrupting immune surveillance. Although the majority of ingested microplastics are excreted via feces, those that enter the bloodstream can reach a variety of organs including the heart, liver, spleen, kidneys, mammary glands, ovaries, uterus, and placenta. ,,− Notably, microplastics have also been found to transiently accumulate near the thyroid, possibly contributing to parathyroid dysfunction and structural damage. Their detection in bone marrow suggests systemic transport via the bloodstream, while renal filtration enables excretion through urine. ,,

Dermal contact represents an important but previously underestimated route of exposure, especially in pregnant individuals. Earlier assumptions about the impermeability of the stratum corneum have been challenged by the identification of nanoscale plastics. In vitro studies demonstrate that nanoplastics can penetrate the stratum corneum, infiltrate hair follicles, and reach dermal capillaries. , Mechanistically, nanoplastics may interfere with protein folding and disrupt membrane lipid dynamics, thereby impairing cellular function. These findings support the plausibility of transdermal absorption. Common products frequently used by pregnant individualssuch as cosmetics, face masks, and synthetic textileshave been identified as key sources of micro- and nanoplastic exposure. − Leave-on cosmetics (e.g., skincare products, foundations, eyeshadows) contain diverse microplastic polymers that remain on the skin for extended periods. A cross-sectional study detected microplastics on both facial and hand skin, with significantly higher levels on female facial skin, largely linked to facial cleanser use. Additionally, emerging evidence suggests that microplastics may reach the endometrium not only through systemic circulation but also via luminal transport along the vaginal–uterine axis.

Respiratory inhalation also constitutes a notable route of microplastic exposure; the predominant contributors are fiber emissions from textiles, furniture, and carpets. , Inhaled microplastics exhibit distinctive propertiessuch as shape, size, and polymer compositionthat vary across indoor and outdoor environments. Indoor air typically contains higher concentrations of polyester microplastics and smaller particles, reflecting the influence of furnishings and household textiles. , Moreover, translocation to the brain via the olfactory bulb has been proposed, raising concerns about potential neurological impacts. The presence detection of microplastics in nasal lavage fluid and sputum suggests entry through the nasal cavity, with deposition in the upper airways and alveoli. , Moreover, translocation to the brain via the olfactory bulb has been proposed, raising concerns about potential neurological impacts and potentially translocation to the brain through the olfactory bulb.

2.2. Microplastics Exposure during Early Life

Early life refers to the critical developmental window from fertilization to two years after birth. Before birth, the primary route of microplastic exposure is transplacental transfer. Studies have shown that microplastics entering the maternal bloodstream via ingestion, inhalation, or dermal absorption can reach the placenta and cross the placental barrier into the fetus. The detection of microplastics in placental and fetal tissues provides strong evidence for this pathway, suggesting it is the most direct and dominant route of microplastic exposure during early life.

Oral exposure is a major pathway for microplastic uptake during early life, representing the predominant postnatal route. Using Raman spectroscopy, Ragusa et al. detected microplastic particles in 24 out of 34 human breast milk samples. These findings, along with subsequent studies, confirm that maternal microplastics can be transferred to offspring via lactation. Some researchers have further suggested that microplastics identified in the brains of neonatal mice may primarily originate from breast milk consumption rather than placental transfer during gestation. Considerable levels of microplastics have also been reported in infant formula and plastic feeding bottles. It is estimated that infants may ingest over 660,000 plastic particles annually through bottle nipples alone. , In addition to dietary intake, infants are also exposed to microplastics through mouthing behaviors involving plastic toys, carpets, and other household items. Notably, microplastics concentrations in infant feces have been reported to be approximately ten times higher than those in adults, indicating a substantially elevated exposure burden during early life.

Inhalation is an important route to microplastic exposure during early life. For infants, primary sources include fibers released from clothing and indoor furnishings. Poor ventilation increases airborne microplastic concentrations, and infants’ prolonged presence in enclosed spaces elevates their exposure relative to adults. Immature physiological barriers make early life populations more susceptible to inhaled particles. Microplastics with aerodynamic diameters (AED) of 5–30 μm tend to deposit in the upper respiratory tract via impaction, while smaller particles deposit in the lower respiratory tract through sedimentation (1–5 μm) and diffusion (<1 μm). Although clearance mechanisms such as sneezing, mucociliary action, phagocytosis, and lymphatic transport exist, their efficiency is reduced in infants due to the immaturity of these systems during early life. This may lead to higher pulmonary retention, inflammation, oxidative stress, and disrupted airway epithelial development. , Dermal exposure is a plausible route to microplastic uptake during early life. Due to the immaturity of the infant skin barrier, microplastics may more readily penetrate and enter the body.

2.3. Evidence for transplacental transfer of microplastics

2.3.1. In Vitro Simulation

The earliest evidence supporting the hypothesis of transplacental microplastic transfer was generated using an ex vivo human placental perfusion model (Table ).

1. Experimental Evidence Related to Transplacental Microplastics Transfer ^,

Different methods	Experimental model	Plastic type	Particle size	Exposure concentration dose	Experimental outcome	Reference
In vitro simulation	Ex vivo dual recirculating human placental perfusion model	PS	50,80,240,500 nm	25 μg/mL	PS beads up to a diameter of 240 nm were taken up by the placenta and, further, were able to cross the placental barrier without affecting the viability of the explant.
	Ex vivo human placental perfusion model	PS	50,240,300 nm	0.02–10 μg/mL	Observed a bidirectional transfer of plain and COOH PS beads up to a size of 300 nm using the ex vivo human placental perfusion model
Animal experiments	Sprague–Dawley rats	PS	20 nm	300 μL (2.64 × 1014 particles)	Nanopolystyrene translocation from the maternal lungs to the fetal compartment and deposition in the fetal, liver, heart, kidney, and brain on GD 20, within 24 h of maternal exposure.
	ICR mice	PE	10–45 μm	0.01 mg/mouse/day, 0.1 mg/mouse/d)	PE-MPs can be detected in different organs of dams and neonates following intragastric administration.
	C57BL mice	PS	100 nm, 1000 nm	1 mg/d	100 nm NPs crossed the placental barrier, entered the fetuses, and emerged in the fetal brain, especially in the thalamus.
	Sprague–Dawley rats	PS	25 nm	250 μg/mL, 10 mL/kg	Large clusters of PS were identified in all gestationally exposed fetal tissues examined, including liver, kidney, lung, heart and brain
	C57BL mice	PS	50 nm	0, 25, 50, 100 mg/kg/d	Doses of 50 or 100 μg/kg indeed induce miscarriage by increasing placental apoptosis in a PS-NPs-exposed pregnant mouse model.
	C57BL mice	PS	6–154 μm	/	MPs were detected in all 13 examined tissues, with preferred depositions in the fetus, placenta, kidney, spleen, lung, and heart.

^aThis table summarizes all experimental evidence related to transplacental microplastic transfer, encompassing vitro simulation, animal experiments. The ex vivo placental perfusion model, as the earliest experimental proof that microplastics can traverse the placental barrier, underscores the feasibility of their transplacental transfer. Animal experiments further elucidate the mechanisms underlying their transplacental transfer and shed light on the associated health risks. “/” denotes the absence of relevant data in the article.

^bThe abbreviations mentioned in the table are as follows. PS, (polystyrene); PE, (polyethylene).

In this system, fluorescently labeled polystyrene (PS) particles of varying sizes (50, 80, 240, and 500 nm) were introduced into a dual-recirculating circuit to assess their ability to cross the placental barrier. Particles with a diameter of 500 nm were largely restricted to the maternal circulation and placental tissue, whereas 240 nm particles were taken up by the placenta and successfully transported to the fetal side without compromising explant viability. Subsequent studies using the same model confirmed bidirectional transport, with PS particles demonstrating more efficient movement from the fetal to maternal side than in the reverse direction. Regardless of the transport direction, all particle sizes were found to accumulate within the syncytiotrophoblast layer, indicating a critical regulatory role for this structure at the maternal–fetal interface.

Importantly, passive diffusion was not identified as the dominant mechanism of transfer. Instead, the transport process appeared to be energy-dependent and possibly involved phagocytosis-like pathways. While the ex vivo perfusion model closely simulates real-world exposure, its application is limited by tissue degradation over time, making it less suitable for evaluating chronic low-dose exposures. Additionally, the perfusion rates in such models reflect late pregnancy conditions, when the placental barrier is thinner and the fetal capillary density is higher. Thus, these rates may overestimate the transport efficiency during earlier gestational stages.

2.3.2. Animal Experiments

To further elucidate the transplacental transport of microplastics, researchers have conducted in vivo experiments using animal models (Table ). Researchers administered 20 nm polystyrene (PS) particles to pregnant rats via intratracheal instillation on gestational day 19. Within 24 h, PS particles were detected in the placenta and fetal organs, including the liver, lungs, heart, kidneys, and brain. This study offered the first in vivo evidence supporting the transplacental transport of microplastics. However, it remains uncertain whether the detected particles were internalized by fetal cells, located in interstitial compartments, or reabsorbed into maternal circulation. In a separate study, mice were orally exposed to microplastic particles of different sizes throughout gestation. Both nano- and micron-sized particles were able to cross the gastrointestinal mucosal barrier, yet only 100 nm particles traversed the placental barrier and accumulated in the fetal brain. In contrast, larger 1000 nm particles were retained within the decidual layer of the placenta. A recent investigation simulating real-world exposure via disposable paper cups demonstrated that microplastic particles smaller than 100 μm could also cross the placental barrier and reach the fetus in pregnant mice. This finding contrasts with earlier conclusions, suggesting that PS particles larger than 100 nm are unable to cross the placenta, highlighting the need for further clarification. While animal studies provide compelling evidence that small-sized microplastics can reach the fetus via transplacental transfer, species-specific differences in the placental structure must be considered. In humans, the maternal–fetal interface consists of a single multinucleated syncytiotrophoblast layer with underlying cytotrophoblasts, which differs markedly from rodent models. Thus, transmembrane transport observed in animals may not fully replicate human conditions.

2.3.3. Evidence of Microplastics Detected in Human Tissue Samples

Detection of microplastics in placental and fetal tissues confirms placental accumulation of microplastics, raising significant concerns about fetal exposure during gestation (Table ). In a study analyzing placentas from six healthy women using Raman spectroscopy and detected microplastic fragments in four samples. The particles primarily composed of colored polypropylene, marking the first direct evidence of microplastics presence in human placentals and suggesting their potential to cross maternal barriers and affect fetal development. In a separate study, analysis of two women who delivered in plastic-free environments revealed polyethylene (PE), polypropylene (PP), and polyurethane (PU) microplastics in their placental and meconium samples. This finding further demonstrates the transplacental transfer of microplastics during pregnancy. However, due to potential contamination during clinical sampling and technical limitations in detecting particles smaller than 50 μm, actual exposure levels may be underestimated. With advances in detection methods, researchers employed more sensitive laser direct infrared spectroscopy (LD-IR) to identify 149 microplastic particles in 17 placental samples. The particles were morphologically classified as fragments, fibers, films, and subspheresof which fragments and fibers accounted for approximately 90%. Notably, the size distribution demonstrated a strong negative correlation between the particle size and abundance, with 80% of particles falling within the 20–100 μm range. This suggests that a substantial number of microplastics smaller than 20 μm may have been undetected, potentially underestimating actual exposure levels. A long-term study in Hawaii reported between 2006 and 2021, the proportion of placental samples testing positive for microplastics increased from 60 to 100%, while the number of detected particles rose from 22 to 82 per sample. These findings are consistent with the global surge in plastic production and environmental contamination, indicating escalating human exposure.

2. Human Biomonitoring Evidence Related to Transplacental Microplastics Transfer ^,

Simple	Detected Microplastic Species	Particle size	Microplastic Abundance	Analysis of Human Samples	Reference
Human placenta	PP and others	5–10 μm	12	Distribution of Microplastics: 5 in fetal side, 4 in maternal side, 3 in membranes
Human placenta and Meconium	PE, PP, PU	>50 μm	/	Microplastics were detected in placental tissue. In addition, analysis of maternal stool samples revealed an average of approximately two polyethylene (PE) and one polystyrene (PS) microplastic particles per 20 g of feces.
Human placenta	PVC, PP, PBS, PET, PC, PS, PA, PE, PAM, PSF	>20 μm	149	All 17 human placenta samples contained detectable microplastics. Polyvinyl chloride (PVC) and polypropylene (PP) were the predominant polymers identified, with most particles being fragments in the 20–100 μm size range.
Human placenta	PE, PS, PET, PP	2.9–34.5 μm	6 and 302	A total of 6 and 302 Microplastics were identified in placentas obtained from pregnancies with normal outcomes and those complicated by intrauterine growth restriction (IUGR), respectively.
Human placenta	PU, PA, PE, PET, PC	20–500 μm	Median MP concentration (particles/g): 18.0	Various types of microplastics (MPs) were detected in placental tissue, meconium, and infant fecal samples.
Human placenta	/	/	/	Ultrathin section analysis of 10 placental samples using transmission electron microscopy (TEM) confirmed the presence of microplastic (MP)-like particles across all compartments of the terminal villi in human term placentas.
Human placenta	PA, PU, PE, PET, PP, PVC, POM, EVA, PTFE, CPE, PC, PS, PMMA, PLA	>20 μm	Placenta: 18.0 particles/g (median)	MPs are ubiquitous in placentas and meconium samples.Particles measuring 20–50 μm accounted for the majority (76.46%) of those detected. Fewer particles were found in the 50–100 μm and 100–150 μm ranges, with those exceeding 150 μm representing the smallest proportion.
			Meconium: 54.1 particles/g (median)
Human placenta	PP, PE, PVC, PU, PVA, PET, PE, PA	2006: average size 2.82  ±  0.31 μm (range: 1–8 μm); 2013: average size 6.24  ±  0.57 μm (range: 1–17 μm); 2021: average size 5.14  ±  0.75 μm (range: 1–44 μm).	146	Microplastic (MP) particles were detected in 6 out of 10 placentas (60%) in 2006, in 9 out of 10 placentas (90%) in 2013, and in all placentas (100%) in 2021.
Human placenta and amniotic fluid	PVC, PE	6.8 μm ∼ 260 μm	Amniotic fluid: 15 MPs	A total of 44 microplastics and additives, comprising 15 different materials, were identified in 20 samples
			Placenta: 28 MPs
Human placenta	PS, PE	/	NMPs: 6.5–685 μg/g, mean  ±  SD = 126.8  ±  147.5 μg/g (placental tissue).	Among 62 placenta samples, Pyrolysis-Gas Chromatography–Mass Spectrometry (Py-GC-MS) analysis revealed the presence of microplastics in all participants’ placentae.
Human placenta	PS	/	0–1.68 mg/kg	PS plastic fragments exist in human villi.
Human placenta	PTFE, PS, ABS, PP, PE, PVC	1.03–6.84 μm	40	Researchers identified 40 microplastic particles in 31 out of 50 placentas, with an average particle size of 2.35  ±  1.25 μm (range: 1.03–6.84 μm).

^aThis table summarizes all available human sample-based evidence supporting the transplacental transfer of microplastics. Compared with experimental models, the detection of microplastics in actual human placental and neonatal fecal samples provides stronger and more direct evidence for transplacental transfer. “/” denotes the absence of relevant data in the article.

^bThe abbreviations mentioned in the table are as follows. (Note: PS, polystyrene; PA, polyamide; PP, polypropylene; PE, polyethylene; PVC, polyvinyl chloride;PU, polyurethane; PET, polyethylene glycol terephthalate; POM, polyoxymethylene; EVA, ethylene vinyl acetate copolymer; PTFE, polytetrafluoroethylene; CPE, chlorinated polyethylene; PMMA, poly­(methyl methacrylate); PLA, polylactic acid; ABS, acrylonitrile butadiene styrene plastic).

Most alarmingly, recent studies utilizing pyrolysis gas chromatography–mass spectrometry (Py-GC-MS) have detected particles as small as 1 μm in placental tissues. This is particularly concerning, as particles below 1 μm have been shown to induce trophoblast apoptosis, potentially increasing the risk of miscarriage and adverse pregnancy outcomes. Future research should focus on the identification of nanoscale microplastics, conduct in-depth evaluations of their toxicokinetic characteristics and developmental toxicity, and comprehensively understand the health risks of microplastic exposure during pregnancy.

3. Effects of Prenatal Microplastics Exposure on Pregnancy

Pregnancy is an important developmental window period and is highly sensitive to environmental pollutants. Maternal exposure to microplastics can not only affect the mother’s own physiological functions but may also allow microplastics to be transferred to the fetus via the placenta or through breast milk, thereby impacting placental function, fetal development, and offspring health. This chapter aims to explore the effects of maternal exposure during pregnancy on both maternal health and offspring birth outcomes (Figure ).

2.

Effects of microplastic exposure during pregnancy on maternal and birth outcomes. Mechanisms by which prenatal microplastic exposure damages maternal ovaries, uterus, and placenta, leading to altered neonatal birth outcomes. The abbreviations mentioned in the figure are as follows.MPs, microplastics; FSH, follicle-stimulating hormone; E2, estradiol; TE, testosterone; SOD, superoxide dismutase; LPO, lipid peroxidation; Wnt/β-Catenin, Wingless/β-catenin signaling pathway; HMGB1, high mobility group box 1; Acetyl-HMGB1, acetylated high mobility group box 1; TLR4, toll-like receptor 4; NOX2, NADPH oxidase 2; IRE1α, inositol-requiring enzyme 1 alpha; JNK, c-Jun N-terminal kinase; GRP78, glucose-regulated protein 78; Bcl-2, B-cell lymphoma 2; Caspase-2, cysteine-aspartic protease 2; Caspase-3, cysteine-aspartic protease 3; TNF-α, tumor necrosis factor-alpha; IL-6, interleukin 6; IL-4, interleukin 4; 11β-HSD2, 11β-hydroxysteroid dehydrogenase type 2; GR-α, glucocorticoid receptor alpha.

3.1. Effects of Maternal Microplastic Exposure on Pregnancy Outcome

With the continuous deepening of research on the reproductive toxicity of microplastics, accumulating evidence suggests that maternal exposure can adversely affect pregnancy outcomes through multiple biological mechanisms. Maternal exposure to microplastics during pregnancy can not only impair ovarian function by causing endocrine disruption through oxidative stress and hormonal imbalance but also damage the structure and immune microenvironment of the uterus and placenta, leading to functional disorders. Oral exposure of pregnant mice to 10 mg/kg/day polystyrene microplastics (PS-MPs) for 45 days can lead to increased levels of follicle-stimulating hormone (FSH), estradiol (E2), and testosterone, indicating endocrine dysfunction. At the same time, it decreases ovarian antioxidant enzyme activity and increases lipid peroxidation levels, resulting in significant oxidative stress. Moreover, 0.5 μm microplastic particles can be internalized by granulosa cells, trigger oxidative stress-induced apoptosis, reduce the number of developing follicles, and activate the Wnt/β-catenin signaling pathway to promote ovarian fibrosis and reduce ovarian reserve function. Microplastic exposure can inhibit oocyte maturation and embryonic development, significantly decrease the first polar body extrusion rate, fertilization rate, and blastocyst formation rates, resulting in reduced embryo quality. Studies have demonstrated that PS-MPs can significantly reduce endometrial thickness and gland numbers along with the occurrence of adhesions and vacuolar degeneration. Furthermore, they can induce uterine fibrosis through HMGB1 acetylation and the TLR4/NOX2 axis, which activates Notch and TGF-β signaling pathways. PS-NPs exposure increased maternal heart weight, impaired aortic endothelial function, and decrease radial artery dilation capacity, leading to vascular dysfunction and thus affecting uteroplacental blood flow and fetal cardiovascular development. Polyethylene microplastics and nanoplastics (PE-MPs and PE-NPs) has also been associated with abnormal umbilical artery flow and disrupted placental hemodynamics. In terms of placental development, microplastics can impaired placental vascularization, significantly reduce the numbers and diameters of uterine arteries in pregnant mice, leading to placental insufficient perfusion and elevated reactive oxygen species (ROS). PS-MPs can also downregulate the expression of tight junction proteins (ZO-1, ZO-2, Claudin-1, Claudin-3), disrupt placental barrier structure, , and decrease placental weight within 24 h. , At the same time, microplastics hinder early pregnancy trophoblast invasion and uterine vascular remodeling by reducing decidual NK cell populations and inducing trophoblast apoptosis through the Bcl-2/Caspase-2/Caspase-3 axis pathway. In addition, microplastics affect the proportion of placental immune cells, promote M2-type macrophage differentiation, increase the proportion of Th cells, and cause imbalance in inflammatory cytokines. They lead to elevated levels of IL-4 and IL-6, and reduced levels of TNF-α, IL-2, and IFN-γ. This imbalance between pro-inflammatory and anti-inflammatory factors may disrupt the inflammatory environment required for embryo implantation during early pregnancy, leading to embryo resorption and pregnancy failure.

At the molecular level, microplastics lead to adverse outcomes by inducing endoplasmic reticulum stress and placental metabolic reprogramming. Microplastics activate the GRP78/IRE1α signaling pathway to induce endoplasmic reticulum stress, which further activates the JNK axis, triggering inflammatory signals and promoting trophoblast apoptosis and inflammatory signaling. Microplastics can also promote autophagic degradation of SOX2 suppress its transcriptional activation of ROCK1, impairing trophoblast invasion and migration, and increasing miscarriage risk. Metabolomics analysis revealed that microplastic exposure upregulates key genes related to placental cholesterol transport (e.g., APOA4 upregulation), leading to cholesterol metabolism disorders. It also disrupts the metabolic pathways of biotin, lysine metabolism, and glycolysis, ultimately resulting in reduced lysine and glucose levels in the placenta and insufficient fetal nutrient supply. , In summary, microplastics impair maternal systems and placental function through multiple mechanisms, and further evaluation is needed to assess their potential long-term risks to pregnancy and fetal development.

3.2. Effects of Prenatal Microplastic Exposure on Birth Outcomes

Increasing evidence suggests that maternal exposure to microplastics during pregnancy may cause fetal growth restriction and reduced birth weight with sex-specific effects. In an analysis of 13 placentas from intrauterine growth restriction (IUGR) cases, microplastics were detected in all samples, while placental samples from normal pregnancies showed levels below the detection limit. This study has raised great concern about microplastic exposure during pregnancy, suggesting that maternal microplastic exposure may be closely associated with fetal developmental disorders. Experimental studies have demonstrated that maternal exposure to 0.5 or 5 mm microplastics during gestation leads to downward trends in offspring birth weight and liver weight, although these differences did not reach statistical significance. In contrast, exposure to 100 nm polystyrene microplastics at 1 and 10 mg/L significantly reduced litter birth weight by 14.72% and 12.03%, respectively, and also resulted in reduced liver and testis weights in offspring. Furthermore, when mice were exposed to microplastics at a dose of 40 mg/kg during pregnancy, it not only significantly reduced offspring birth weight but also decreased postnatal survival rates on both postnatal day 7 and day 21. Beyond fetal growth restriction and mortality, several studies have indicated that these adverse outcomes exhibit significant sex differences. Maternal exposure to microplastics during pregnancy can alter the sex ratio of offspring at birth. One study showed that after pregnant mice were exposed to high doses of polyethylene microplastics, the proportion of male offspring significantly increased. Two independent studies confirmed that fetal developmental disorders and reduced birth weight have clear sex-dependent effects. Birth weight in females significantly decreased, whereas no significant changes were observed in males. , This phenomenon may be linked to placental vascular injury, as PS nanoparticle exposure resulted in disrupted vascular spaces and decreased red blood cell counts specifically in female placentas. Additionally, placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) mRNA expression was markedly decreased in female fetuses, while glucocorticoid receptor-α (GR-α) expression was significantly upregulated.

The adverse effects of microplastics on birth outcomes may result from the combined action of multiple molecular mechanisms. These mainly include placental metabolic disorders, oxidative stress, inflammation, and immune imbalance. Placental metabolic disorders are an important mechanism by microplastic-induced fetal growth restriction. In high-dose exposure groups, placental expression of CD36a key fatty acid transporterwas significantly increased, alongside upregulation of genes involved in triglyceride synthesis, collectively impairing placental nutrient delivery. In addition, during pregnancy, microplastic particles can be transported via maternal circulation to multiple fetal organs such as the liver, lungs, heart, kidneys, and brain, which may be potentially reason for reduced organ and body weight after birth.

Additionally, maternal microplastic exposure can induce oxidative stress and inflammatory responses in the placenta, which may impair energy supply, compromise trophoblast function, and exacerbate immune imbalance. ,,,,, These may lead to immune imbalance, thereby increasing the risk of miscarriage, fetal growth restriction, and preterm birth. In summary, the mechanisms by which microplastics induce developmental toxicity during pregnancy are complex. However, current research is mainly based on animal models, and due to the complexity of microplastic size, the diversity of material types, and the difficulty in accurately assessing real exposure doses, their extrapolation to human populations is limited. Future studies should focus on establishing standardized exposure models and conducting more population-based research to provide scientific evidence for health risk assessment in pregnant individuals.

4. Effects of Microplastics on Fetal Development and Offspring Health

Growing evidence suggests that microplastics can cross the placental barrier and accumulate in the fetal body during pregnancy. After birth, infants are continuously exposed to microplastics through various routes, including breastfeeding, baby bottles, and mouthing plastic toys. Compared to adults, infants face a heightened risk of microplastic exposure because their organs are not fully developed, underdeveloped metabolic and excretory functions, and increased susceptibility to environmental contaminants. While previous sections have addressed maternal exposure and its implications, this section shifts the focus to offspring, highlighting both in utero and postnatal impacts of microplastic exposure on fetal development and early life health.

4.1. Effects on Offspring Development and Reproduction

Among the various toxicological effects of microplastic exposure, its adverse impact on reproduction and development is particularly alarming. , Maternal exposure to 1 or 10 mg/L polystyrene nanoplastics significantly reduced the liver size and weight in offspring at postnatal day 21. Pathological analysis reveals sinusoidal congestion, inflammatory infiltration, and pronounced architectural disruption of hepatic lobules. Despite the absence of direct exposure, prenatal microplastic exposure also led to decreased testicular weight, reduced sperm count and motility, and altered testicular gene expression in male offspring. In female offspring, oocyte maturation and fertilization rates were diminished, impairing subsequent embryonic development. Both sexes exhibited disrupted amino acid metabolism and carnitine homeostasis, potentially increasing the risk of fatty acid metabolic disorders and associated pathologies.

Compared with exposure during pregnancy, postnatal microplastic exposure presents even greater risks to offspring owing to more diverse exposure pathways. In male offspring, microplastic exposure compromised the blood–testis barrier (BTB), a key structure that maintains the integrity of the spermatogenic environment. Microplastics disrupt the cytoskeletal organization and alter the expression of actin-binding proteins and tight junction proteins, leading to damage of the BTB structure. In this process, testicular structure was damaged, resulting in exfoliation of spermatogenic cells, disorganized arrangement of spermatogenic cells, and the presence of multinucleated glandular cells within the seminiferous tubules, which is indicative of severe pathological changes. These impairments led to decreased sperm count, reduced motility, and increased malformations, including acrosome loss, microcephaly, acephaly, neck bending, and tail detachment. Furthermore, microplastics that accumulate in the testes can dysregulate the hypothalamic–pituitary–testicular (HPT) axis, leading to the suppression of gonadotropins (GnRH, LH, FSH) and reduced testosterone secretion. At the same time, microplastics disrupts the expression of DAZL and PLZF genes further impairs germ cell proliferation and differentiation, thereby exacerbating spermatogenic failure. , In female offspring, early life microplastic exposure delayed vaginal opening and increased anogenital distance (AGD), suggesting delayed development of reproductive organs. The estrous cycles of mice became disordered, likely due to disturbances in sex hormone secretion, resulting in a shortened estrous cycle and prolonged luteal stages. Moreover, female mice demonstrated decreased oocyte quality, ovarian dysfunction, impaired embryonic development, , and hormonal imbalance following microplastic exposure. In conclusion, microplastics impair offspring development across multiple organs and exhibit marked sex-dependent effects. The underlying mechanisms involve structural damage to reproductive organs, disrupted metabolic pathways, endocrine imbalance, and impaired germ cell development.

4.2. Effects of Microplastics on Neurodevelopment and Behavior in Offspring

The World Health Organization (WHO) has identified mental disorders as a growing global public health burden. Emerging evidence indicates that the brain may serve as a major target for microplastic (MP) accumulation, raising concern about their potential neurotoxic risks. Studies have confirmed the presence of MPs in the brain and highlighted multiple pathways for their deposition. During embryogenesis, MPs can be translocated from the maternal circulation to the fetal brain via transplacental transfer. ,, Postnatally, the maturing blood–brain barrier (BBB) limits MP entry. However, experimental evidence suggests that MPs can cross the BBB, either by disrupting tight junctions such as VE-cadherin or through direct transcytosis, particularly in the case of nanoscale particles. − Discrepancies remain regarding the size threshold for the BBB penetration. Some studies report that particles as large as 2–5 μm may cross the BBB under certain conditions, , while others indicate that even 1 μm particles show limited permeability. Inhaled MPs may bypass the BBB altogether by accessing the brain through the olfactory nerve and distributing via synaptic connections. Once inside the brain, MPs can induce structural damage. Maternal exposure to polystyrene (PS) MPs has been shown to affect the composition of neural cells by inducing neural stem cell dysfunction. This ultimately results in reduced cortical plate thickness in offspring mice, excessive proliferation of superficial neurons, and a decrease in deep-layer neurons, indicating selective impairment of specific neuronal subtypes. ,, Microplastic exposure also results in dendritic spine loss and decreased dendritic complexity, potentially linked to downregulated brain-derived neurotrophic factor (BDNF) and inhibition of the CREB/BDNF signaling cascade. Microglia readily internalize MPs and initiate inflammatory responses through the PERK-NF-κB pathway, releasing TNF-α and IL-1β, which aggravate neuronal injury. , Additionally, MPs impair microglial autophagy and energy metabolism, disrupting synaptic pruning and altering synaptic density. Dysregulation of glutamate metabolism via the liver–brain axis may further impair cerebellar Purkinje cells and motor coordination.

Microplastic exposure not only causes damage to brain structures but also leads to significant neurotransmitter disturbances and induces behavioral abnormalities in offspring mice. Neurotransmitter changes accompany structural damage. In MP-exposed offspring, levels of dopamine, serotonin, acetylcholine, GABA, and oxytocin were significantly reduced. ,,, These disruptions were associated with anxiety-like behavior, social deficits, and cognitive impairments. Such behaviors may result from neuroinflammation triggered by TLR and NF-κB signaling, vagus nerve-mediated oxytocin disruption, and impaired synaptic protein expression, including PSD-95 and synaptophysin. ,,, Additionally, gut–brain axis signaling may activate microglia via IL-1, further contributing to memory impairment and cognitive decline. , Taken together, these findings underscore a potential link between early MP exposure and increased susceptibility to neurodevelopmental and neurodegenerative disorders. , In conclusion, microplastics may cross the blood–brain barrier through multiple pathways, accumulate in the brain, and interfere with neurodevelopment in offspring, leading to behavioral abnormalities and an increased risk of neurodevelopmental disorders.

4.3. Effects on Offspring Immune System Development

The immune system serves as a critical defense mechanism responsible for recognizing and eliminating foreign invaders. However, microplastics (MPs), upon entry into biological systems through oral, respiratory, or dermal exposure, can accumulate in various tissues and interfere with immune equilibrium. Recent studies have demonstrated that MPs induce oxidative stress and inflammatory responses while impairing immune cell viability, triggering dysregulation of immune signaling pathways and ultimately promoting systemic immune imbalance. , Upon exposure, the immune system fails to efficiently eliminate these persistent synthetic particles, leading to a prolonged inflammation. MPs activate the NF-κB and MAPK pathways, elevating intracellular reactive oxygen species (ROS) levels and enhancing the secretion of pro-inflammatory cytokines such as IL-6 and TNF-α. − Additionally, MPs released from food packaging materials can be internalized by macrophages, reducing cell viability and impairing lysosomal function. These effects are linked to mitochondrial dysfunction, sustained mitophagy, lysosomal stress, and subsequent rupture, resulting in calcium release and the formation of macrophage extracellular traps (METs), which are novel inflammatory mechanism. In immune-compromised mouse models, MP exposure further aggravated intestinal inflammation, altered gut microbial communities, and downregulated tight junction proteins, implying impaired gut-immune integrity. Transcriptomic and metabolomic analyses following 49-day exposure to nanoplastics revealed disruption in genes related to lipid metabolism and neuroactive ligand–receptor interactions, further supporting immune perturbation at the systemic level.

In addition, studies have found that microplastic exposure also induces sex-dependent immune alterations. In a subacute oral exposure model using polyethylene (PE) MPs, no significant changes in thymic or splenic T or B cell subpopulations were detected. However, a marked decrease in the IgG2a/IgG1 ratio indicated a shift toward Th2-type immunity, particularly in females. In contrast, lactational exposure to polystyrene (PS) MPs in male mice resulted in increased spleen weight, expansion of B cells and regulatory T cells, and a bias toward Th1 and Th17 responses. These findings are consistent with previous studies reporting Th1-skewed responses in males exposed to PE MPs. Although female offspring showed no significant change in Th subsets, RT-PCR analysis revealed suppressed expression of genes related to T-helper cell differentiation, suggesting transcriptional-level modulation. The immune outcomes appeared independent of particle size within the tested range (5–24 μm), yet smaller nanoplastics are believed to elicit stronger immunotoxic effects.

Collectively, these findings demonstrate that MPs disrupt immune homeostasis by promoting pro-inflammatory responses, altering Th1/Th2 balance, and impairing immune cell functionality. The extent of immunotoxicity is influenced by particle size, chemical composition, and the potential for MPs to act as vectors for environmental pathogens. The transgenerational effects of microplastics on the immune system and their impacts under chronic exposure further highlight the complexity of their role as environmental threat.

5. Mechanisms of Microplastic Toxicity during Pregnancy and Early Life Exposure

Previous sections highlighted the main routes of human microplastic exposure and their impact on pregnancy and fetal development. Given the heightened vulnerability during early life stages, understanding the underlying mechanisms of microplastic toxicity is crucial for effective risk assessment and early intervention. This section examines three interrelated pathways through which microplastics may exert developmental toxicity: (1) oxidative stress and inflammation, (2) endocrine disruption, and (3) epigenetic alterations. These mechanisms can impair embryogenesis, disrupt placental and fetal organ function, and contribute to long-term health risks. Elucidating these pathways may facilitate the identification of sensitive biomarkers and support the development of preventive strategies during critical developmental windows (Figure , Figure ).

3.

Mechanisms of microplastic toxicity during early life exposure. Early life exposure to microplastics induces inflammation, oxidative stress, and endocrine disruption, leading to lipid peroxidation, cell apoptosis, autophagy, and pyroptosis. MPs trigger pancreatic cell apoptosis, lipid accumulation, thyroid dysfunction, and reduced testosterone synthesis. Moreover, MPs modulate noncoding RNAs and epigenetic modifications (DNA methylation and histone modification), further affecting neurodevelopment and metabolic homeostasis. The abbreviations mentioned in the figure are as follows. PS, polystyrene; PE, polyethylene; PLA, polylactic acid; SOD, superoxide dismutase; MDA, malondialdehyde; ROS, reactive oxygen species; TNF-α, tumor necrosis factor-alpha; IL-1β, interleukin-1 beta; NLRP3, NOD-like receptor protein 3; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; Caspase-1, cysteine-aspartic protease 1; BSA, bovine serum albumin; DEHP, di­(2-ethylhexyl) phthalate; GRP78, glucose-regulated protein 78; CHOP, C/EBP homologous protein; Bcl-2, B-cell lymphoma 2; AMPK, AMP-activated protein kinase; ULK1, unc-51 like autophagy activating kinase 1; PAX8, paired box gene 8; CREB, cAMP response element-binding protein; IP3R, inositol 1,4,5-trisphosphate receptor; PTH, parathyroid hormone; TSH, thyroid-stimulating hormone; LHR, luteinizing hormone receptor; cAMP, cyclic adenosine monophosphate; PKA, protein kinase A; STAR, steroidogenic acute regulatory protein; miR-1a-3p, microRNA-1a-3p; circRNA_SM6G, circular RNA SM6G; PTEN, phosphatase and tensin homologue; MMPs, matrix metalloproteinases; DNMT1, DNA methyltransferase 1; DNMT3A, DNA methyltransferase 3A; BPA, bisphenol A; Jhdm2a, jumonji domain-containing protein 2A; CYP11A1, cytochrome P450 family 11 subfamily A member 1; 17β-HSD, 17β-hydroxysteroid dehydrogenase.

4.

Mechanisms of microplastic toxicity during pregnancy exposure. Maternal exposure to polystyrene microplastics (PS) during pregnancy induces inflammation, oxidative stress, and mitochondrial dysfunction, accompanied by endocrine disruption. These effects impair oocyte maturation, trophoblast cell migration, and placental function, further leading to insulin resistance, glucose metabolism disorders, and reproductive hormone imbalance in offspring. The abbreviations mentioned in the figure are as follows. PS, polystyrene; IL-4, interleukin 4; TNF-α, tumor necrosis factor-alpha; MDA, malondialdehyde; GST, glutathione S-transferase; ROS, reactive oxygen species; ATP, adenosine triphosphate; MFN1, mitofusin 1; OPA1, optic atrophy 1; DRP1, dynamin-related protein 1; M1/M2, macrophage type 1/2; CAT, catalase; GSH-Px, glutathione peroxidase; PI3K, phosphoinositide 3-kinase; Akt, protein kinase B; mTOR, mammalian target of rapamycin; SOX2, SRY-box transcription factor 2; ROCK1, Rho-associated coiled-coil containing protein kinase 1; GPX1, glutathione peroxidase 1; PERK, PKR-like ER kinase; EIF2α, eukaryotic translation initiation factor 2-alpha; ATF4, activating transcription factor 4; CHOP, C/EBP homologous protein; SRD5A2, steroid 5 alpha-reductase 2.

5.1. Inflammation and Oxidative Stress

Inflammation and oxidative stress are recognized as central mechanisms in microplastic-induced toxicity, particularly in the context of maternal and fetal exposure. Inflammation, a critical physiological defense response to external insults, is closely interlinked with oxidative stress, which arises from the excessive production of reactive oxygen species (ROS). Numerous studies have demonstrated that microplastic exposure significantly elevates intracellular ROS levels, overwhelms antioxidant defense systems, and induces lipid peroxidation, DNA damage, and cellular dysfunction. ,,, Oral administration of polystyrene (PS) microplastics, especially in nanoparticle form, leads to heightened oxidative stress through two primary routes: direct interaction with lipid membranes and intracellular release of toxic components. In maternal exposure models, increased malondialdehyde (MDA) levels and decreased superoxide dismutase (SOD) activity have been observed in offspring tissues, including the liver and testes, indicating a redox imbalance and enhanced oxidative burden. Elevated oxidative stress biomarkers have also been detected in the placenta, fetal liver, and brain, reinforcing the systemic nature of the oxidative insult. ,, Mitochondria, as the primary energy-generating organelles, are particularly vulnerable to oxidative damage. Mitochondrial integrity is essential for oocyte development, fertilization, and early embryogenesis. Microplastic-induced ROS disrupt mitochondrial membrane potential, impair ATP synthesis, and lead to functional collapse of mitochondrial networks. A 30 day exposure to PS microplastics has been shown to downregulate key mitochondrial dynamics genes, including MFN1 and OPA1 (fusion markers) and DRP1 (a fission marker), reflecting impaired fusion–fission homeostasis. Moreover, structural and functional disturbances in mitochondria–endoplasmic reticulum (ER) tethering have been reported, exacerbating mitochondrial and ER stress. ,

In parallel, microplastics trigger inflammatory responses through multiple signaling cascades. Activation of the NF-κB and NLRP3 inflammasome pathways promotes the release of pro-inflammatory cytokines such as IL-1β and TNF-α, accompanied by changes in macrophage and T cell activity. Sustained NF-κB signaling amplifies NLRP3 expression and activates Caspase-1, driving GSDMD cleavage and facilitating pyroptotic cell death, characterized by plasma membrane rupture and the release of inflammatory contents. ,,, These findings underscore that microplastic exposure not only compromises redox balance but also initiates inflammation-driven tissue injury, thereby disrupting maternal-fetal homeostasis during critical developmental periods.

5.2. Endocrine Disrupting Potential

Beyond oxidative stress and inflammation, microplastics (MPs) and their associated additives exert endocrine-disrupting effects by interfering with hormone production, secretion, and receptor signaling. Once internalized, MPs can release lipophilic endocrine-disrupting chemicals (EDCs), including di­(2-ethylhexyl) phthalate (DEHP) and bisphenol A (BPA), which disturb endocrine homeostasis. Co-exposure to PS-MPs and DEHP exerts synergistic toxicity, activating the GRP78/CHOP/Bcl-2 axis in pancreatic cells via oxidative stress, thereby inducing apoptosis and impairing endocrine pancreas function. Recent evidence has highlighted the role of MPs in dysregulating lipid and glucose metabolism. PS nanoplastics trigger lipophagy through the AMPK/ULK1 signaling pathway, which promotes the autophagic engulfment of lipid droplets. This leads to lysosomal dysfunction and impaired lipid turnover, contributing to hepatic lipid accumulation and increasing the risk of metabolic diseases such as NAFLD and liver fibrosis. Short-term MP exposure elevates blood glucose and activates compensatory metabolic regulators; however, prolonged exposure results in pancreatic accumulation of MPs, disrupting insulin secretion, and causing hypoglycemia. MPs impair insulin signaling by inhibiting the PI3K/AKT pathway, leading to insulin resistance and glucose metabolism imbalance. In addition, MPs also affect thyroid and parathyroid function. MPs alter thyroglobulin synthesis via PAX8 and CREB signaling, suppress TSH production from the pituitary gland, and cause thyroid hormone imbalance. In the parathyroid, MPs downregulate Mafb and IP3R expression, reducing PTH secretion and disrupting calcium signaling, which may affect bone and mineral homeostasis.

In male reproductive health, MPs accumulate in the testes and are internalized by Leydig cells. This induces GPX1 degradation via miR-425-3p and ubiquitin pathways, triggering ER stress through the PERK-eIF2α-ATF4-CHOP cascade. CHOP, in turn, promotes SRD5A2 transcription, accelerating testosterone metabolism and reducing serum testosterone levels. Additionally, MP exposure drives macrophage polarization toward the M1 phenotype, leading to NF-κB activation in Leydig cells and downregulation of luteinizing hormone receptor (LHR), impairing the LHR/cAMP/PKA/StAR pathway. MPs also disrupt GnRH release in the hypothalamus, suppressing LH and FSH production and further impairing the HPT axis. In summary, microplastics disrupt endocrine function in offspring mice by releasing endocrine disruptors, impairing metabolic and thyroid homeostasis and interfering with reproductive hormone regulation through multiple signaling pathways, thereby increasing long-term health risks.

5.3. Epigenetics

Epigenetic alterations represent a pivotal mechanism underlying microplastic (MP)-induced developmental toxicity, particularly during gestation and early life. MPs can interfere with gene expression through DNA methylation, histone modifications, and noncoding RNA (ncRNA) regulation. DNA methylation is a fundamental epigenetic process. Exposure to polyethylene (PE) MPs increases global DNA methylation in a dose-dependent manner, with elevated methylation observed in both adult and offspring testicular tissues following maternal exposure. ,, Moreover, MPs act as vectors for endocrine-disrupting compounds such as bisphenol A (BPA), which upregulates DNA methyltransferases (DNMT1 and DNMT3A), enhancing methylation of metabolism-related genes and contributing to reproductive dysfunction. , Histone modifications regulate the chromatin accessibility and transcriptional activity. Polystyrene (PS) MPs reduce H3K9me1/2 and H3K4me2/3, while increasing H3K9me3 in the testesalterations associated with transcriptional repression. PS MPs also upregulate Jhdm2a, a demethylase targeting H3K9me2, which facilitates the expression of key steroidogenic genes (e.g., CYP11A1, 17β-HSD) and enhances testosterone synthesis.

NcRNAs, especially microRNAs and circular RNAs (circRNAs), play critical roles in post-transcriptional regulation. MPs downregulate miR-1a-3p, disrupting cytoskeletal remodeling via twinfilin-1 suppression, contributing to pulmonary fibrosis. In the brain, PS MPs alter synapse-related miRNAs in the prefrontal cortex, disturbing ceRNA networks essential for neural development. Moreover, MPs modulate circRNA profiles; suppression of circRNA_SMG6 activates the miR-570-3p/PTEN/MMPs pathway, promoting emphysematous changes.

In conclusion, MPs can induce multilayered epigenetic abnormalities that may exert transgenerational and long-lasting effects on the reproductive, metabolic, and nervous systems. This also provides new insights for exploring corresponding early biological markers in future research.

6. Conclusion and Future Perspectives

The health risks of microplastic (MP) exposure during pregnancy and early life have become an issue that cannot be ignored. Microplastic particles in the environment can enter the body through the digestive tract, respiratory tract, and skin and can be transferred across the placenta into the fetus. Newborns may not only ingest MPs through breast milk but also face a higher exposure risk. Pregnancy and early life are highly sensitive developmental windows. MPs can induce reproductive and developmental toxicity through multiple mechanisms, including oxidative stress and inflammation, endocrine disruption, and epigenetic modifications, leading to maternal physiological dysfunction, fetal developmental abnormalities, and adverse birth outcomes. Moreover, MPs can exert transgenerational effects, further increasing health risks to the nervous, immune, metabolic, and reproductive systems of the offspring. This indicates that MP exposure can interfere with the entire developmental process of newborns during critical stages and can alter their lifelong health trajectory. However, current research on MPs still has significant limitations. Most experimental studies are based on high doses, single particle types, and animal or in vitro models, which cannot realistically simulate chronic low-dose mixed exposure in real-life human environments. There remains a lack of a systematic and authoritative understanding of the distribution and metabolic processes of MPs with different sizes, shapes, and chemical compositions in the body. The detection methods and standardized quantification techniques for nanoscale MPs are still largely absent, making it difficult to determine the true level of human exposure. Toxicological mechanism studies mostly focus on single pathways or specific organs, lacking multilevel and systematic integrative analyses. Constructing corresponding adverse outcome pathways is urgently needed. In addition, the absence of large-scale human epidemiological data makes it difficult to extrapolate experimental results to population-level health risks.

In addition, there is significant heterogeneity and potential bias in microplastic quantification across different studies. The heterogeneity mainly arises from variations in sample sources (such as human tissues and environmental matrices), the lack of standardized definitions for particle morphology and size (for instance, there is no unified definition for the size range of nanoplastics), and differences in the physicochemical properties of various polymers. At the present, no universally accepted analytical method has been established. The potential biases primarily result from background contamination caused by instruments or personnel, matrix interference due to incomplete or excessive digestion of biological tissues, chemical pretreatment errors (particularly for degradable or heat-sensitive polymers), and inconsistencies in statistical approaches (such as discrepancies between manual and automated identification or between particle number and concentration units).

Future research on MPs should shift from isolated mechanistic studies to more realistic and systematic investigations. First, more sensitive and standardized detection technologies should be established to identify the environmental behavior and ADME processes of MPs of different types and sizes. Second, unified standards for size classification and identification methods should be established, and standardized detection protocols applicable to different sample types and biological matrices should be developed to reduce the methodological variability and improve data comparability among studies. Third, large-scale epidemiological studies should be expanded to explore real-world exposure scenarios and integrate existing findings to construct adverse outcome pathways. Finally, interdisciplinary collaboration among materials science, toxicology, and clinical medicine should be strengthened to improve MP health risk assessment systems and provide a scientific basis for microplastic pollution control and health protection policies.

Haopeng Zhang: Methodology, Formal analysis, Validation, Writing - original draft,Visualization. Xiaomeng Ding, Huijuan Zheng, Qianweng Ma: Resources, Writing - review and editing, Supervision. Ting Zhang: Conceptualization, Funding acquisition, Project administration, Writing - review and editing.

The authors declare no competing financial interest.