Concerning influences of micro/nano plastics on female reproductive health: focusing on cellular and molecular pathways from animal models to human studies

Abstract

The female reproductive system can face serious disorders and show reproductive abnormalities under the influence of environmental pollutants. Microplastics (MPs) and nanoplastics (NPs) as emerging pollutants, by affecting different components of this system, may make female fertility a serious challenge. Animal studies have demonstrated that exposure to these substances weakens the function of ovaries and causes a decrease in ovarian reserve capacity. Also, continuous exposure to micro/nano plastics (MNPs) leads to increased levels of reactive oxygen species, induction of oxidative stress, inflammatory responses, apoptosis of granulosa cells, and reduction of the number of ovarian follicles. Furthermore, by interfering with the hypothalamic-pituitary-ovarian axis, these particles disturb the normal levels of ovarian androgens and endocrine balance and delay the growth of gonads. Exposure to MNPs can accelerate carcinogenesis in the female reproductive system in humans and animal models. Animal studies have determined that these particles can accumulate in the placenta, causing metabolic changes, disrupting the development of the fetus, and endangering the health of future generations. In humans, the presence of micro/nanoplastics in placenta tissue, infant feces, and breast milk has been reported. These particles can directly affect the health of the mother and fetus, increasing the risk of premature birth and other pregnancy complications. This review aims to outline the hazardous effects of micro/nano plastics on female reproductive health and fetal growth and discuss the results of animal experiments and human research focusing on cellular and molecular pathways.

Introduction

Reproductive health, as one of the most important indicators of quality of life, is strongly related to the condition of the human reproductive system and can be changed under the influence of many factors [1, 2]. Infertility, which refers to the failure to develop a pregnancy after 12 months of regular unprotected sex, currently affects the lives of 50 to 80 million women [3]. According to WHO reports, female factors contribute to about 37% of infertility problems, while male factors account for about 29%, and combined female and male factors account for about 18% of the causes. The remaining 16% are genetic factors or unexplained or idiopathic infertility [4, 5]. The female reproductive system, in addition to controlling the development of secondary sexual characteristics, is also the location of gametogenesis and secretion of sex hormones and embryo development [6]. Any impairment in the function and even the structure of this system can lead to reproductive disorders such as premature puberty, abnormal cycle, premature ovarian insufficiency/menopause, endometriosis, fibroids, and adverse pregnancy outcomes and eventually cause this system to fail in females [7, 8]. Some of the damages inflicted on the female reproductive system may result from biological pollutants, which can stem from various sources such as medications, agricultural chemicals, chemicals found in cosmetic and hygiene products, and food items [9].

Currently, due to their versatility, durability, and cost-effectiveness, plastic materials are considered the most widely used substance globally. However, these substances are permanent pollutants in every ecological part of the world [10]. Bottles, bags, disposable materials, and untreated wastewater are among the most common and main sources of plastics [11, 12]. The term microplastics (MPs) was used in 2004 to describe microscopic plastic particles in the marine environment [13] and finally, microplastics were defined as particles 100 nm to 5 mm, and nanoplastics (NPs) were defined as particles less than 100 nm. These small particles are classified into two categories, MPs and NPs, which are collectively known as micro (nano) plastics (MNPs) [10, 14]. These particles with different sizes, colors, and shapes are found in freshwater, soil, air, and some food products [15,16,17]. Plastics and small particles resulting from them damage the ecosystem and all life on earth, especially human health, and continuous exposure to these substances, including MNPs, can be the main source of diseases and disruption of human fertility [18].

In recent years, the negative effects of MNPs on fertility have been widely investigated in animal models. Evidence shows that MNPs cause reproductive toxicity by disrupting the structure and function of the uterus, ovaries, and endocrine glands as well as the hypothalamus-pituitary axis [19, 20]. Exposure to these polluting particles causes fibrosis in these organs through the accumulation of reactive oxygen species (ROS) and the activation of the relevant signaling pathways [21, 22]. Induction of oxidative stress, inflammation, apoptosis, and malignancy in the reproductive organs of females can affect the process of ovulation and generally put their fertility and health at risk [23]. By inducing apoptosis in granulosa cells and also reducing the number of ovarian follicles, these substances change the levels of androgens in this organ and then disrupt the reproductive endocrine system [24].

In human studies, the negative effects of MNPs on women’s fertility have received much attention in recent years. The available evidence points to a significant relationship between continuous exposure to MNPs and the reduction of women’s fertility [25, 26]. These substances, by accumulating in human reproductive organs and exerting toxic effects, can compromise their function [27]. It has been shown that these pollutant particles can damage cell components through intracellular pathways and disrupt the cell cycle [28]. MNPs, in addition to maternal damage, during pregnancy and lactation by passing through the placenta and penetrating various organs of the fetus, including the heart, liver, lungs, and spleen [29], and affecting their reproductive and nervous systems, cause transgenerational toxicity and disturb the embryonic development [30, 31]. The invasion of these particles into the human trophoblast and the change of gene expression in its cells can lead to common disorders in the immune system of the mother and the fetus [32]. Following the suppression of the mother’s immune system due to exposure to these substances, the risk of miscarriage increases, and the mother’s health is also endangered [33]. The toxic effects of MNPs, as well as the vulnerability of the female reproductive system to these exogenous substances, have raised concerns about female fertility and focused much attention on the identification of these environmental hazards [34]. This review aims to describe the harmful impacts of micro/nano plastics on various aspects of female reproductive system and discuss the animal and human research focusing on cellular and molecular mechanisms.

Effects of microplastics and nanoplastics on reproductive health: evidences from animal studies

Microplastics and nanoplastics, as toxic substances, can accumulate in reproductive organs and disrupt the reproductive capacity of various animal species [35]. So far, numerous studies have been conducted on various animals and animal models regarding the effects of microplastics on the female reproductive system, summarized in Table 1. In male rats, MNPs could enter the lumen of the seminiferous tubule by disrupting the integrity of the blood-testis barrier (BTB) and reducing the number of seminiferous epithelial cells and Sertoli cells [19, 36, 37]. Acute exposure to polystyrene nanoplastics (PS-NPs) in mouse Sertoli cells causes the destruction of BTB through the destruction of tight junction proteins and the reduction of antioxidant capacity [38, 39]. BTB damage may lead to further disruption of the internal structure of the spermatogenic tube including lumen atrophy and hyperplasia [19, 40], which can lead to testicular histological changes, abnormal spermatogenesis, and serum hormone secretion interference in mice [20]. The effect of MNPs on testosterone secretion is dose-dependent [41] and various studies show that exposure to NPs can significantly reduce luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels [19, 20, 41]. In addition, MNPs can enter testicular cells, including Leydig cells, Sertoli cells, and spermatogonia, and cause the production of large amounts of ROS. Studies have shown that NPs increase the production of ROS by disrupting the function of the mitochondrial membrane, which causes more damage to the mitochondria [36, 42,43,44]. Exposure to MNPs through the gastrointestinal (GI) tract causes apoptosis in mouse sperm cells at all stages, and on the other hand, it can also lead to an inflammatory response in that area by stimulating the migration of T helper 17 cells in the testis [41, 45,46,47]. Long-term exposure to NPs, by inhibiting the autophagy system, can cause serious damage to the cell and also lead to the formation of abnormal acrosome [40, 48]. Finally, it can be mentioned that for male, the damage caused by microplastics includes the creation of the abnormal structure of the testicles and sperm, reduction of sperm life, and endocrine disorders caused by oxidative stress, inflammation, apoptosis of testicular cells, autophagy, abnormal cytoskeleton, and abnormal axis of hypothalamus-pituitary-testis [49].

Table 1 Effects of microplastics on the animal reproductive system

In females, exposure of the GI tract to MNPs can reduce the ovarian mass-to-body mass ratio, the number and volume of growing follicles, and antral follicles. It can also lead to a reduction in the thickness of the granular layer of secondary follicles or a decrease in granulosa cell count. Also, exposure to MNPs can increase ovarian fibrosis, primary cysts, and atretic follicles and affect female ovarian reserve and fertility [21, 24]. By damaging the structure of the uterus and endometrium, as well as narrowing the uterine glands, these substances can cause embryo implantation to fail [22, 55, 57]. Also, exposure to MPs can be an indirect reason for abortion by disrupting the balance in maternal immunity during pregnancy [33]. MNPs GI tract exposure, also by decreasing the level of estradiol and progesterone and increasing the level of LH and FSH in the serum, causes disorders in female endocrine glands [24, 52]. The effects of exposure to MNPs are dose-dependent and can increase oxidative stress by reducing the level of antioxidant enzymes and increasing the level of lipid peroxide [21, 51, 52]. Also, MNPs increase inflammation by increasing the level of inflammatory cytokines and decreasing the level of anti-inflammatory cytokines, thereby disrupting the structure of the ovary and uterus and endocrine function [46, 47, 76]. So, exposure to MNPs is associated with a decrease in the number and diameter of small uterine arteries and a reduction in endometrial thickness, leading to implantation failure. These small particles can also induce oxidative stress, inflammation, increased apoptosis, and even malignancy in the female reproductive system (Fig. 1). The transfer of NPs from the mother’s body to the fetus can accumulate in their various tissues, including the brain, liver, lungs, kidneys, and heart, causing disturbances in metabolism, reproductive function, immune function, neural development, and cognitive function [77, 78]. Also, maternal exposure to MNPs can cause transgenerational toxicity and premature death in children [49, 79].

Fig. 1

The effects of micro/nano plastics against the female reproductive system. Accumulation of MNPs in the tissue of the uterus and ovaries leads to oxidative stress, inflammation, and apoptosis in the cells of these tissues, and by weakening the function of these organs, it disrupts their efficiency. In uterine tissue, the reduction of implantation rate can be one of the serious consequences of exposure to MNPs. These plastic particles may also cause ovarian tissue epithelial cells to become cancerous

Impacts of microplastics and nanoplastics on the female reproductive system: a focus on animal models

Studies conducted on animals have shown that MNPs, as hazardous particles, can affect the female reproductive system in various ways. The impacts of these substances have been thoroughly examined, particularly in animal models. By changing its structure, MNPs disrupt the normal function of reproductive system components, including the uterus and ovaries. The structural changes of the uterus can have extensive effects on female reproductive health by disrupting the implantation of the embryo [80]. This change in the structure and function of the ovaries may have unintended consequences, including a decrease in egg production or the creation of non-viable eggs, as well as disruption of the ovulation process [49]. MNPs can reduce the size and number of oocytes by activating or suppressing different signaling pathways, and also decrease the number of follicles in the ovaries, thereby affecting ovulation in the female reproductive cycle [25]. Since follicles and granulosa cells are crucial for hormone production and oocyte development, their loss leads to hormonal imbalance [81]. Exposure to MNPs increases LH, FSH, and testosterone levels while decreasing estradiol and progesterone, potentially leading to female infertility [24]. Additionally, exposure to MNPs by increasing the level of ROS and inducing oxidative stress increases the level of collagen and fibronectin in the uterine tissue, contributing to the progression of tissue fibrosis in this organ [49]. The accumulation of ROS in both ovaries and the uterus leads to increased expression of proteins associated with fibrosis and tissue damage [22]. Exposure to MNPs increases the level of inflammatory cytokines and decreases the level of anti-inflammatory cytokines, indicating the adverse effects of these substances on ovarian and uterine tissues [82]. Lower doses of MNPs temporarily enhance the expression of antioxidant enzymes by activating signaling pathways such as Nrf2/ARE. However, higher doses or prolonged exposure to MNPs inhibit these pathways, intensify oxidative stress, and promote ovarian fibrosis [83]. Also, exposure to high levels of MNPs may trigger inflammation and disrupt the immune system [84]. These substances also affect fertility by inducing gene mutation in gametes [85]. In mice, long-term exposure to MNPs causes a decrease in the quality of oocytes and an increase in cell apoptosis in the endometrium. In general, MNPs can accumulate in reproductive organs and, by inducing oxidative stress, apoptosis, reducing the number of follicles, and affecting the hormonal profile, have significant impacts on reproductive health [32, 49]. In the following, we will thoroughly assess and detail the harmful effects of MNPs on the female reproductive system in animal models.

Function and structure of ovaries and uterus

One of the main causes of infertility in females is dysfunction of the uterus and ovaries [46]. Exposure to polystyrene microplastics (PS-MPs) can disrupt female reproductive performance and fertility by causing damage to uterine and ovarian structures [24, 49]. Several studies have shown that MNPs GI tract exposure reduces the number and volume of growing follicles in the ovaries [21, 24, 52, 55] and causes a decrease in the thickness of the granular layer in secondary follicles and also reduces the number of granulosa cells and corpus luteum. On the other hand, these substances can increase ovarian fibrosis and primary cysts [21, 46, 51]. Also, exposure to MNPs reduces the number of antral follicles and increases the number of atretic follicles in the ovaries, which can ultimately affect female ovarian reserve and fertility [57, 86]. In a study, zebrafish that were treated with PS-MPs for 1 to 3 weeks showed the absence of oocyte-follicular cell layer linkage and oocyte vacuolation [63]. It has also been reported that gavage of rats with a certain dose of 5 μm PS-MPs leads to disturbance of the cytoskeleton by reducing the expression of dishevelled associated activator of morphogenesis 1 (DAAM-1) and α-tubulin in ovarian cells [51]. On the other hand, exposure of mice to different doses of PS-MPs with a size of 40–48 μm showed dilation of the abdominal aorta and fallopian tubes [56].

According to reports, MNPs GI tract exposure, by reducing the number and diameter of small uterine arteries and reducing the thickness of the endometrium, causes damage to the structure of the uterus and endometrium and in turn, disrupts the implantation of the fetus [52, 79]. Also, MNPs can lead to uterine fibrosis, narrowing of the uterine glands, and the density of its extracellular matrix [22, 49]. In one study, the histopathological examination of the uterus of mice exposed to a combination of PS-MPs and Pb showed a decrease in uterine glands and glandular lumen thickness and an increase in the number of atretic follicles and interstitium density. In addition, the thickness of the endometrium in these mice was significantly reduced with the loss of glands and lamina propria structures [52]. It has been shown that in Oryzias melastigma, a combination of PS-MPs and phenanthrene can inhibit ovarian maturation and increase the risk of follicular atresia [87].

The weight of the reproductive organs is an indication of the growth, health, and function of the reproductive system [88]. Exposure to PS-MPs significantly reduces the growth coefficient of the body and organs of the uterus and ovary, as well as the uterus and ovary coefficient in female mice [24, 52]. On the other hand, oxidative stress caused by exposure to MPs can cause histological abnormalities in ovaries such as vacuolation in ooplasm, granulosa cells and interstitial cells, corona radiata disorder, and micronuclei formation in the egg nucleus [25]. Also, PS-MPs weaken the function of ovaries by reducing the level of FSH and can cause infertility in females [24]. Exposure of female mice to Bisphenol A, which is used in the manufacture of various plastics, also causes ovarian cysts and stromal polyps [89].

The ovulation process

The number of eggs produced is the main indicator to evaluate the functioning of the ovaries [90]. Environmental pollutants can have adverse effects on germ cells and the overall process of reproduction during maturation or egg formation [91]. Studies have shown that exposure to MPs affects the quality of eggs by increasing the production of ROS, disrupting oocyte maturation, and inducing apoptosis, and subsequently, reducing the blastocyst rate, fertilization, and fertility [57, 58]. MPs can reduce oocyte production through Wnt/β-Catenin and NLRP3/Caspase-1 signaling pathways, and in addition to reducing the number and size of oocytes, it also reduces their survival rate [62, 92]. Several findings have shown that PS-NPs can significantly increase apoptosis and necrosis in oocytes after several generations and by destroying the spindle structures or actin assembly, they can disrupt the meiotic maturation of oocytes [21, 46, 58, 59]. Also, exposure to PS-MPs decreases the first polar body extrusion rate, glutathione (GSH) level, mitochondrial membrane potential, and endoplasmic reticulum calcium ([Ca²⁺]ER) in oocytes [57].

It has been found that exposure to PS-MPs leads to atrophy of the corpus luteum and eventually to a decrease in its number. Also, these substances play a role in reducing the growth and total number of ovarian follicles and can cause the production of empty follicles [24, 39, 66]. In confirmation of these findings, Haddadi et al. reported that PS-MPs can lead to altered folliculogenesis in rats [51]. In a study on zebrafish, it was found that exposure to a combination of PS-MPs and 17α-Methyltestosterone (MT) leads to vacuolization and a decrease in mature oocytes, as well as loss of communication between eggs and follicular cell layers, and this damage, becomes more severe over time. In addition, this decrease in the number of mature oocytes may occur due to the decrease in LH and FSH levels [63]. Estradiol, acting as a steroid hormone, inhibits apoptosis in granulosa cells and luteal cells, leading to follicular maturation and ovulation. However, its levels decrease under the influence of MPs [24, 93]. Furthermore, following external ovarian stimulation, female mice exhibited a reduced likelihood of ovulated oocytes, with a higher proportion of cumulus-free oocytes retrieved from the oviducts [94].

Female sex hormones and endocrine disorders

The development, maturity, and function of the female reproductive system are influenced by the endocrine system, which regulates the appropriate hormone levels for the proper functioning of reproductive processes [95]. As the main functional units of ovaries, follicles, and granulosa cells produce sex hormones and other growth factors required for oocyte development. Therefore, the loss of these cells causes a disturbance in the level of sexual and reproductive hormones [24, 96]. Estradiol (E2), as a steroid hormone, inhibits apoptosis in granulosa and luteal cells and regulates follicular maturation and ovulation [93, 97]. Granulosa cell apoptosis can lead to endocrine disorders. These cells play a crucial role as the primary producers of E2. When E2 levels decrease due to granulosa cell apoptosis, it triggers a chain reaction. This includes an increase in LH and FSH levels, mediated by negative feedback from the hypothalamic-pituitary-ovarian (HPO) axis. Consequently, this disruption in the endocrine system occurs [24, 51, 97, 98].

By accumulating in the reproductive organs and through the induction of oxidative stress and apoptosis, MPs disrupt the function of the endocrine glands as well as the reproductive system [11, 99, 100]. PS-MPs can enter hormone-producing cells in the ovaries and reduce the number of follicles [101]. These substances also affect the steroid synthesis pathway through the Hypothalamic-pituitary-gonadal (HPG) axis and then affect the reproductive endocrine system [102, 103]. During several studies, it was found that after MNPs GI tract exposure, serum LH, FSH, and testosterone levels increased in female rats, but serum E2 and progesterone levels decreased significantly, which could weaken ovarian function, and eventually lead to female infertility [24, 51, 52, 55]. Also, exposure to MNPs reduces the level of sex steroid hormones such as 17β-estradiol, hatching rate, and gamete formation in Oryzias melastigma, and by disrupting the HPG axis, it affects the development of ovaries and the female reproductive system [66].

MNPs may contain environmental endocrine-disrupting chemicals (EDCs), which are a group of compounds with hormone-like biological effects and can disrupt the endocrine balance by affecting the secretion and metabolism of sex hormones [104, 105]. Exposure of female zebrafish to PS-MPs and 17α-Methyltestosterone (MT) as an EDC for 7 days increased the expression of cyp19a1a mRNA in the ovaries, which in turn plays a role in the conversion of testosterone to estrogen. MT may disturb the hormonal balance in the body by increasing the level of testosterone and upregulating cyp19a1a mRNA and causing an increase in serum E2 level [63, 106]. On the other hand, Rong et al. reported that exposure to a certain dose of PS-MPs, MT, and PS-MPs + MT for 14 days caused a significant decrease in the levels of LH, FSH, and E2 in female zebrafish ovaries [63]. A decrease in the level of LH and FSH, as key factors in regulating the level of expression of steroid hormones, reduces the number of mature ovules and delays the growth of gonads [63, 107, 108]. Also, a study on oysters has shown endocrine disruption in exposure to PS-MPs [62]. Long-term exposure to PS-MPs and MT often exacerbates hormonal imbalance by inhibiting the genes responsible for steroid hormone production and blocking their synthesis [63]. Also, exposure to PS-MPs along with Pb causes more severe damage to the follicles and causes a further decrease in the level of progesterone and E2 [52].

Triggering oxidative stress

The main toxicity caused by exposure to MNPs is increased ROS accumulation and induction of oxidative stress [109]. Oxidative stress can be described as an imbalance between the production of reactive oxygen species and the body’s ability to deal with it [110], which can affect egg quality and fertility. Exposure to MPs causes oxidative stress in the female reproductive system by increasing the level of ROS [58]. Oxidative stress caused by contact with MPs appears in a dose-dependent manner [49]. Investigations revealed that exposure of the GI tract to MNPs resulted in increased levels of reactive oxygen species in the ovarian tissue of rats. Concurrently, there was a decrease in the levels of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and total antioxidant capacity (TAC), while the levels of lipid peroxide and malondialdehyde (MDA) also increased [22]. While lower doses of MPs GI tract exposure (e.g. 0.1 mg/day) lead to an increase in the level of antioxidant enzymes such as SOD, and CAT, this increase is probably due to the activation of the Nrf2/ARE signaling pathway. In fact, as a result of oxidative stress, Nrf2 is separated from keap1 in the cytoplasm and after phosphorylation and transfer to the nucleus, it connects to the ARE part of the promoter of CAT and SOD genes and increases the expression of these enzymes [51, 111]. These findings are supported by reports indicating that the level of Nrf2 and its downstream proteins increases after exposure of ovarian granulosa cells to MPs for one day. However, with an increase in MPs dosage or exposure time, the Nrf2 signal is inhibited, and the levels of antioxidant enzymes decrease, intensifying oxidative stress [51, 55]. The accumulation of ROS in the ovary, by increasing the expression of the main proteins involved in the Wnt/β-catenin signaling pathway, causes more activity of this pathway and more β-catenin transfer to the nucleus of ovarian fibroblasts, and in the same way, the expression of transforming growth factor-β (TGF-β), α-smooth muscle actin (α-SMA), increase fibronectin and other protein factors related to fibrosis and eventually cause ovarian fibrosis [21].

Toll-like receptor (TLR4)/NOX2 signaling pathway can increase ROS production and then oxidative stress in different stress conditions. It has been reported that in the uterine tissue of female rodents exposed to MPs, the activation of Notch and TLR4 pathways and the production of ROS, followed by the increase of collagen and uterine proteins, cause uterine fibrosis [22]. PS-MPs by increasing the expression of high mobility group box 1 protein (HMGB1) and acetyl-HMGB1, which act as TLR4 ligands, cause the activation of this receptor, followed by the activation of NOX2, and finally by triggering the TLR4/NOX2 signaling pathway increases ROS and aggravates oxidative stress [22, 112]. The increase in ROS caused by exposure to MPs in the uterus increases the expression of a disintegrin and metalloproteinase kinase (ADAM kinase), γ-secretase, and Notch protein ligands (Delta and Jagged) and activates the Notch signaling pathway, which this pathway can directly increase the level of fibronectin and collagen and indirectly through cross-talk with TGF-β/Suppressor of Mothers against Decapentaplegic 3 (Smad3) signaling pathway may be involved in uterine fibrosis [22]. Indeed, following the activation of Notch signaling, the notch intracellular domain (NICD) increases the transcription of genes involved in fibrosis by transferring to the nucleus and interacting with DNA binding protein CSL. In addition, NICD can increase the activity of the TGF-β/Smad3 signaling pathway through direct interaction with phosphorylated Smad2/3, and thus increase the expression of proteins involved in fibrosis such as collagen, α-SMA, matrix metalloproteinases-2/9 (MMP2/9) and Hes family [22, 113] (Fig. 2). Inhibitors of TLR4/ NADPH oxidase 2 (NOX2) and γ-secretase signaling can effectively prevent increased ROS, Notch activation, collagen expression, and uterine fibrosis [22, 114, 115]. Experimental results have shown that PS-MPs can induce pyroptosis and apoptosis in ovarian granulosa cells through the NLRP3/Caspase-1 signaling pathway, which can be related to oxidative stress and the loss of its antioxidant capacity, and increase the risk of female infertility [46]. It has been found that co-exposed to PS-MPs and Pb, through the protein Kinase RNA-Like ER Kinase (PERK)/Eukaryotic initiation factor-2α (eIF2α) signaling pathway, causes oxidative stress and ovarian toxicity and reduces the number of follicles and oocyte quality in mouse ovaries [52].

Fig. 2

Molecular pathways involved in the increase of fibrosis in the ovary and uterus by exposure to micro/nano plastics. The occurrence of fibrosis in the ovary and uterus can be caused by the accumulation of MNPs in these tissues. By increasing the expression of HMGB1, MNPs cause the activation of NOX2 after activating the TLR4 receptor, which ultimately increases the expression of Notch ligands by increasing the level of ROS and ultimately leads to the activation of the Notch signaling pathway. Through cross-talk with the TGF-β signaling pathway and the effective transfer of p-SMAD2/3 to the nucleus, this pathway activates the expression of collagen, α-SMA, MMP2/9, and Hes family, increasing the collagen fibers in the ECM. Also, the activation of the Wnt/β-catenin signaling pathway as a result of exposure to MNPs, with the effective transfer of β-catenin to the nucleus, increases the expression of TGF-β, followed by the increase of collagen in the ECM of the cell which eventually causes fibrosis in the uterus and ovaries

Inflammation and reproductive aging

Exposure to high amounts of MPs may cause damage to the nervous system, followed by inflammation and disruption of the immune system [84]. Studies have shown that MPs can induce oxidative stress, inflammatory responses, and finally gene mutation in gametes and reduce fertility in animals [85, 116]. Oxidative stress with ion influx and cell lysis leads to the release of IL-18, IL-1B, and other inflammatory cytokines [82, 117]. Increased levels of inflammatory cytokines such as IL-1β, IL-6, IL-8, IL-18, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) in serum, ovary, and uterine tissues [21, 57] and also the decrease in the level of anti-inflammatory cytokines such as IL-4, IL-10, and IL-13, are the main signs of inflammation caused by exposure to MPs [22]. TLR4, as a toll-like receptor, can stimulate the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) with the help of tumor necrosis factor receptor-associated factor 6 (TRAF6) and ultimately cause the release of inflammatory factors. MPs, such as polyethylene microplastics (PE-MPs), can increase the amount of ROS in ovaries and stimulate TLR4 receptors, causing the TLR4/TRAF6 signaling pathway and TRAF6 ubiquitination and then activate inhibitor of κB kinase (IKK) and finally cause the activity of NF-κB transcription factors [22, 118]. NF-κB, by regulating the transcription of precursor mRNAs, causes the production of inflammatory cytokines such as IL-1β, IL-6, and TNF-α, and also through the NLRP3 inflammasome pathway, by activating caspase-1, it leads to the transformation of pro-IL1β and pro-IL-18 into mature IL-1β and IL-18, respectively, and thus cause pro-inflammatory responses [46, 47, 76, 119]. Liu et al. showed that exposure of mice to PS-MPs for 35 days can lead to inflammation and reduced oocyte quality [57]. Also, MPs can cause severe apoptosis of epithelial cells and inflammatory responses in the endometrium [120]. In general, MPs can cause inflammation in the uterus and ovaries through the induction of oxidative stress and subsequently affect female fertility [49].

Although inflammation is considered a defense response, this process can also be harmful to body cells and tissues [49]. Inflammatory cytokines and reactive oxygen species can disrupt estrous cycles and steroidogenesis and, in addition, prevent meiotic and cytoplasmic maturation of the oocyte [121]. Also, inflammation can lead to ovarian aging and ultimately reproductive aging in females [122]. Reproductive aging in women is defined by a gradual decline in the number of follicles and the quality of oocytes, which can lead to the loss of fertility and ovarian function. Inflammatory processes have been suggested as potential contributors to this decline [123, 124]. An animal study showed that the decrease in follicle numbers over the reproductive lifespan was associated with an increase in the percentage of CD⁴⁺ T cells, B cells, and macrophages within the ovary. Serum concentrations and intra-ovarian mRNA levels of several pro-inflammatory cytokines, including IL-1α/β, TNF-α, IL-6, and inflammasome genes ASC and NLRP3, also significantly increased with age [122]. Furthermore, oxidative stress, as one of the consequences of micro/nanoplastics, has been reported to act as an initiator of oocyte aging and reproductive pathology [125].

Cellular damage and apoptosis

MPs can cause apoptosis, DNA damage, and autophagic cell death by inducing oxidative stress and inhibiting metabolic pathways [126]. Long-term exposure to PS-MPs can induce apoptosis and pyroptosis in ovarian granulosa cells through the NLRP3/Caspase-1 signaling pathway, which is caused by oxidative damage. In fact, with the increase of oxidative stress, NLRP3 inflammasome is activated after the phosphorylation of NF-κB and causes the activation of caspase-1 through the factors involved in this pathway. Finally, caspase-1 leads to pyroptosis and apoptosis of ovarian granulosa cells by converting pro-IL-1β and pro-IL-18 to IL-1β and IL-18 [46]. It has been shown that exposure of Caenorhabditis elegans to PS-MPs can have deleterious effects on the reproductive system through induction of apoptosis and DNA damage. The researchers found that exposure of these nematodes to PS-MPs for 28 days could change the expression of genes related to apoptosis, such as ced-3, ced-4, and ced-9, and lead to the induction of apoptosis in them [60]. In a study, it was found that exposure of rats to PS-MP particles with a size of 0.5 micrometers and concentrations of up to 1.5 mg/kg per day led to various serious complications, including the induction of cell apoptosis, cell death in the ovary, and reduction of ovarian reserve capacity, excessive proliferation of ovarian fibroblasts, as well as the accumulation of extracellular matrix [46, 101]. It has also been found that the rate of early apoptosis in the oocytes of mice exposed to MP is significantly increased compared to normal oocytes [58]. Hou et al. reported that in rats exposed to 0.5 μm PS-MPs at a dose of 0-1.5 mg/kg/day, apoptosis and death of ovarian cells and hyperproliferation of ovarian fibroblasts were observed [46, 101]. Also, PS-MP particles can be deposited in the granulosa cells of the ovaries of female mice and induce pyrolysis and apoptosis in these cells [46]. Exposure to MPs can disrupt oocyte maturation and affect the quality of oocytes by excessive production of ROS followed by increased apoptosis [58]. Oxidative stress can lead to ER stress [127]. ER stress occurs as a result of increased protein synthesis, changes in calcium homeostasis, and ultimately the accumulation of unfolded or misfolded proteins in the ER lumen [128, 129]. Long-term ER stress can cause reproductive system disorders through apoptosis [130]. Exposure to PS-MPs along with Pb causes an increase in unfolded and misfolded proteins and finally increases the level of binding immunoglobulin protein (BIP) in the ovaries. To prevent ER stress and maintain ER homeostasis, ER transmembrane proteins including PERK, activating transcription factor 6 (ATF6), and inositol-requiring enzyme type 1 (IRE1) are separated from the Bip chaperone, and by activating the relevant signaling pathways, they increase protein folding and remove misfolded proteins [52, 131]. On the other hand, unfolded protein response (UPR) induces apoptosis through the PERK/CHOP signaling pathway. Active PERK causes the activation of ATF4 and increases the expression level of CHOP through the phosphorylation of eIF2α. Exposure to PS-MPs together with Pb increased the expression of PERK, ATF4, eIF2α, and CHOP and therefore induced ER stress through the PERK/eIF2α/CHOP pathway [132,133,134,135].

Tu et al. (2023) showed that in Drosophila, continuous exposure of developing oocytes to 10–100 mg L^-1 PS-NPs in five generations caused apoptosis and necrosis as well as reduced oocyte production. Polystyrene nanoplastics have caused significant changes in the transcription of genes related to reproduction, metabolism, lifespan, and apoptosis in Drosophila and thus affect their reproductive capacity [59]. Buffy is a B cell lymphoma-2 (Bcl-2)/Ced-9-like and pro-survival protein in Drosophila [136]. Overexpression of Buffy increases apoptosis caused by γ radiation and exposure to PS-NPs causes apoptosis and necrosis of ovaries by regulating the expression level of buffy [59]. In a study on zebrafish, it was found that PS-NPs with 70 nm diameter cause behavioral changes, and the accumulation of these nanoparticles in gonads leads to apoptosis of germ cells and disruption of the reproductive system [137].

MNPs and cancers of the female reproductive system in animal models and human studies

Exposure to MNPs can accelerate the progression of carcinogenesis in certain types of cancer [138,139,140]. To support tumor growth and development, tumor cells produce significant cellular and molecular changes in their host tissue, and this change in the tumor microenvironment plays an important role in cancer development [141, 142]. Studies have shown that PS-NPs can accelerate the growth of epithelial ovarian cancer (EOC) tumors in animal models. In vivo experiments on mice showed that exposure to PS-NPs through drinking water increased tumor weight and volume and accelerated tumor growth. These NPs can change the tumor’s microenvironment by influencing the expression of genes and disrupting the cell’s metabolic pathways, leading them to become cancerous. Also, it was shown that PS-NPs can strongly affect pathways related to immune responses and thrombomodulin regulators. These molecular changes can play an important role in accelerating the growth of ovarian cancer [54]. In addition, PS-MPs have been shown to increase apoptosis and oxidative stress, which are known to be key factors in cancer growth and spread, in ovarian tissues, hence, it can be considered as a background for ovarian cancer. The Keap1/Nrf2/HO-1 pathway, known as a key regulator of cellular antioxidant responses and playing a crucial role in protecting cells against oxidative stress, can be disrupted by MPs, especially PS-MPs. This disruption leads to an increase in ROS, causing extensive damage to DNA and other vital cellular molecules, ultimately triggering carcinogenic processes. However, long-term exposure to PS-MPs can promote the formation and progression of ovarian cancer through the induction of oxidative stress and apoptosis [143, 144].

Recent studies have shown that MNPs exist in human tissues including cervical tumors. Specifically, one study reported that MPs from polystyrene, polyvinyl chloride, and polyethylene were detected in 17% of cervical tumor samples [145]. The presence of MPs can change the tumor’s immune microenvironment and affect therapeutic responses. Therefore, these findings can create new challenges in cancer treatment [146]. On the other hand, these nanoplastics can cause inflammation, oxidative stress, and cell dysfunction. These disorders may lead to genetic changes and faulty signaling that ultimately increase the risk of developing cancer, including cervical cancer. In addition, NPs can transport toxic substances into cells, which can seriously endanger human health [147]. Over time, as these NPs accumulate in the body, the risk of developing cancer also increases [148]. Although MNPs at low concentrations may have negligible negative effects on cells, at higher concentrations, they can cause cytotoxicity and induce them to become cancerous [149]. Also, long-term exposure to NPs may lead to chronic inflammation and changes in cells that are associated with an increased risk of cancer [150]. NPs may inadvertently penetrate cells and, by accumulating in tissues, exert toxic or stimulatory effects that can contribute to cancer growth [151, 152]. Polyethylene glycol is also a plastic compound that may exist as environmental MNPs. Its widespread use in nanotechnology and medical treatments raises concerns about the long-term stability of these materials in the body and their potential links to health issues, including cancers [153, 154].

The influence of microplastics and nanoplastics on the placenta and fetal development

Animal models

In this section, the effects of microplastics and nanoplastics on the female reproductive system and fetal growth in animal models are described. This content includes the effects of these particles on the placenta, fetus, and the health of future generations. MPs can be absorbed and accumulated in the placenta in a size-dependent manner, and by affecting embryonic development, it can lead to failure in reproduction [58]. The exposure of mothers to PS-NPs can cause the transfer of these substances to the tissues of the placenta and fetus and disrupt the growth and development of the fetus [29, 155]. Wan et al. (2024) used 50 nm PS-NPs to determine the effect of MNPs on trophoblast cells. They reported that PS-NPs induced abortion in pregnant mice and also suppressed rho-associated, coiled-coil-containing protein kinase 1 (ROCK1)-mediated migration and invasion in these cells. ROCK1 can reduce miscarriage by preventing the formation of migrasome, which is formed as an organelle after the migration of cells. It was found that exposure to PS-NPs caused suppression of SOX2-mediated ROCK1 transcription by activating autophagy and increasing autophagy degradation of SOX2 and eventually, affect the mother and fetus’s health by increasing the risk of abortion [156].

Recently, researchers found that maternal exposure to PE-MPs, despite causing increased blood flow in the fetal umbilical artery and consequently disrupting the normal function of the placenta, does not alter fetal growth. This may be due to the lower toxicity of PE-MPs compared to other MNPs such as PS-NPs and their impact on placental and fetal growth in late pregnancy. The increased blood flow in the umbilical artery could be due to the higher extraction of oxygen from the mother’s blood to sustain fetal growth, which is an adaptive response to compensate for the toxic effects of these pollutant particles [157]. Also, in another study, it was found that although MPs increase blood flow in the umbilical artery, NPs decrease blood flow in this artery. These results show that MNPs cause impaired placenta function, which is strongly dependent on the size of these particles [158].

In addition, significant changes in placental metabolism due to exposure to MPs have been reported, such that exposure to high concentrations of 5 µM PS-MPs caused a significant decrease in the relative concentration of placental lysine and glucose, and cause disturbances in glycolysis, gluconeogenesis, biotin metabolism, and lysine degradation [159]. Also, PS-NPs disrupt cholesterol metabolism in the placenta and fetus and show significant metabolic disorders by affecting the concentration of sucrose and daidzein as well as complement and coagulation cascade pathways. On the other hand, these nanoparticles also affect the expression level of genes related to inflammation and iron homeostasis [160, 161].

NPs reach fetal tissues within 24 h after maternal exposure but are removed from fetal circulation before birth. The health of children after birth and adulthood is affected by the deposition of these particles in fetal tissues during its development [29]. Also, PS nanoparticles can cause abnormal cell morphology in both placenta and fetus [161]. It has been found that exposure to PS-MPs can reduce the fertility rate and the number of embryos and lead to abnormal conception and affect the formation of the embryo. PS-MPs also affect the fertility of male and female mice, reducing the survival and growth of embryos. It should be noted that the fertility of female mice is more affected by these substances than male mice [24, 62, 162].

Exposure of male and female mice to MPs, in addition to causing changes in sex ratio and body weight in the offspring, can also disrupt the metabolism of lipids and amino acids in the offspring and affect the health of the next generation [56, 163]. While MPs increase the level of ROS in oocyte, blastocyst, and embryo, by inducing oxidative stress, they increase apoptosis in embryonic cells and decrease the level of GSH in these cells [58]. To treat this condition, N-acetylcysteine (NAC) has been proposed as an antioxidant to reduce the oxidative damage caused by PS-MPs [83]. Oxidative stress caused by gestational and lactational MPs exposure in mice can also cause damage in their offspring [58].

The passage of NPs through the blood-placenta barrier (BPB) and their transfer via breast milk to offspring are the two main pathways through which offspring are exposed to nanoplastic particles [29, 78], and the transfer of these materials through the placenta depends on their size [164]. Exposure of mother mice to NPs during pregnancy and lactation can cause deposition of these nanoparticles in the intestine, liver, brain, lungs, kidney, and heart tissues of the next generation mice and disrupts their immune system, nervous system, metabolism, and reproduction [29, 77, 78].

After mother’s exposure to MPs, glycolipid metabolism was reduced by the oxidative inhibition of fatty acids in the offspring, which is probably due to the reduction of carnitine levels in them. In addition, lipids were accumulated in the liver for a longer period of time and the absolute weight of the children’s liver was greatly reduced due to inflammatory infiltration and oxidative stress [79, 163, 165]. It has been observed that when the mother is exposed to MPs during pregnancy, the weight of the testes in their male offspring is reduced and disorganized arrangement occurs in their spermatocyte layers [79]. By disrupting the homeostasis of the children’s immune system, these substances cause a decrease in T cells and an increase in Th cells in their spleen and can also inhibit the maturation of dendritic cells [56].

MPs disrupt the balance and function of maternal and fetal immune systems and increase the number of T cells in the placenta; Also, they suppress the immune system by reducing the ratio of pro-/anti-inflammatory cytokines and ultimately indirectly increase the risk of miscarriage [33]. Recent studies show that exposure to MPs during pregnancy and early development in mice can lead to neurodevelopmental problems in the offspring. This includes defects in brain development, impaired brain function and metabolism, and cognitive impairment [79]. Although both MPs and NPs can accumulate in the placenta, only NPs can cross the BPB and enter the fetal brain, especially the thalamus, and disrupt the fetal brain development by inducing oxidative stress and inhibiting the production of γ-aminobutyric acid (GABA) [53].

Also, PS nanoparticles caused anxiety-like behaviors in eight-week-old offspring of mice, which can eventually lead to neurobiological disorders. It was found that the use of glutathione supplementation can reduce oxidative stress and apoptosis caused by PS-MPs in neuronal cell lines [53]. MPs also affect neural stem cells, prevent normal neural growth, and lead to reduced cell proliferation and abnormal production of glial cells in the hippocampus. These substances also change gene expression patterns in neural stem cells and lead to defective neurogenesis by reducing genes involved in cell division and proliferation [78].

In female offspring, MPs exacerbate cognitive dysfunction during brain development. In addition, prenatal and early postnatal exposure to MPs leads to decreased dopamine transporter protein, impaired glucose metabolism, altered gene expression, and autism-like behaviors in offspring and parental exposure to MPs exacerbates these neurodevelopmental disorders in offspring [79]. It has also been determined that the heart rate index of the middle cerebral artery in fetuses exposed to MNPs decreases significantly, which is caused by dilation of cerebral circulation vessels, a type of fetal adaptation preserve oxygen delivery. As a result, exposure to NPs during pregnancy can lead to adverse neurodevelopmental outcomes by causing hypoxia and impaired placental function and fetal brain development [158]. A summary of studies on placentas and fetuses of different animals that were affected by exposure to microplastics and nanoplastics is summarized in Table 2.

Table 2 The influence of microplastics on various fetal structures and organs

Human studies

Here, we discuss the effects of microplastics and nanoplastics on the placenta, fetus, and other tissues related to female human reproductive system. MPs can enter the food chain and disperse as airborne particles, so involuntary ingestion and inhalation are not out of the question. Due to their small size, MNPs and especially NPs can pass through the digestive epithelium and be absorbed by the body. Although it is believed that only 0.3% of these particles can be absorbed, it has been determined that particles with a size of less than 10 micrometers enter the placenta by passing through the cell membrane and cause toxicity in the fetus [171,172,173]. Embryonic cells are very vulnerable to toxicity due to intense and regulated proliferation, differentiation, apoptosis and migration during organogenesis, and any disturbance in the growth, proliferation, and differentiation of cells before and after birth can lead to adult-onset disease [174, 175]. Exposure of pregnant mothers to nanoplastics can damage the developing fetal brain. These particles can cross the placental barrier, causing neuroinflammation, oxidative stress, and disruption of signaling pathways. These effects may lead to defects in brain development, cognitive impairments, and motor disorders [164, 176,177,178,179] (Fig. 3). However, these particles can cause developmental toxicity by accumulating in the placenta and damaging it, which may overshadow the health of the mother during pregnancy in addition to the health of the fetus [180]. Epidemiological data showed that preeclampsia, premature birth, stillbirth, and spontaneous abortion can be the results of exposure of pregnant mothers to (ultra)fine particles [180, 181].

Fig. 3

Schematic representation of the impact of micro/nano plastics on the fetus, offspring, and its various organs. Maternal exposure to MNPs causes the accumulation of these particles in placenta tissue, but among them, only NPs can pass through the BPB and affect different fetal organs. These particles disrupt the fetal immune system and show their negative effects on this organ by increasing inflammation and oxidative stress as well as reducing liver absolute weight. MNPs particles have disturbed the growth and development of the heart and the brain, it leads to a decrease in the expression of genes related to cell division in the hippocampus, and on the other hand, inhibits thalamic GABA synthesis and causes problems in brain development. Also, disturbance in metabolism and reproductive system in both sexes is one of the results of exposure to these harmful particles

Exposure to MPs results in placental growth disorders, oxidative stress and inflammation, activation of placental-like receptors (TLRs) and changes in hormone secretion [92]. Also, the absorption of MPs in the villous tissues, which are the main tissues of the placenta for the exchange of nutrients between the mother and the fetus, may significantly increase the risk of miscarriage [32]. So far, the presence of MNPs in placenta samples, meconium, infant feces, and breast milk samples has been reported [182]. Based on the studies, MPs with a size of approximately 5 to 10 μm were observed in placental tissue and chorioamniotic membranes [30, 163]. Also, the presence of 11 different types of MPs in placenta tissue has been identified, among which polyvinyl chloride (PVC)-MP has the largest share [183]. Grafmueller et al. showed that all PS-MPs accumulate in the placental syncytiotrophoblast, indicating transport of MPs in an energy-dependent manner in the placenta [184].

Examining the placenta tissue in several studies has shown the accumulation of MNPs particles in this tissue. Using Raman microspectroscopy, researchers revealed the presence of 12 MPs fragments in the placentas of 6 women [30]. Also, in confirmation of these findings, in another study, the existence of MPs in the tissue of 17 human placentas was evaluated and it was determined that polypropylene, polyvinyl chloride and polybutylene succinate particles with a size of 200–307.29 μm can accumulate in the placenta [183]. Amereh et al. showed the presence of MPs such as PE and PS in the placentas of 43 women who agreed to have their pregnancies checked for the presence of microplastics (2 to 38 particles per placenta). The results showed that these pollutant particles, which were mostly smaller than 10 μm in size, may cause disturbances in the mutual relations between the placenta and the fetus through disruption of gas and nutrient exchange [185].

Also, placental tissue analysis using pyrolysis-gas chromatography and mass spectrometry showed the presence of 12 types of MPs with different concentrations in this tissue that PE, PVC and nylon constituted the majority respectively [179]. In another study, the measurement of MPs in placenta, meconium, infant feces, breast milk, and infant formula samples of 18 cases, showed 16 types of MPs with an average size of 20–50 μm, with polyamide and polyurethane constituting the majority. Scrub cleaners, toothpaste, food bottles and plastic toys were also introduced as sources of exposure for these pregnant women and infants to MPs [182, 186]. In addition, MPs and plastic additives have also been observed in the amniotic fluid of women who experienced preterm prelabor rupture of membranes [187]. On the surface of villi containing MPs in placentas collected from some women, oxidative stress, cell death, and inflammatory reactions were observed [30].

Infants are at greater risk from these particles due to their insufficient production of metabolizing enzymes and reduced ability to eliminate MPs [188]. The heart, as a fetal organ targeted by MNPs, can face developmental disorders under the influence of these substances. By disrupting the differentiation of cardiomyocytes from human embryonic stem cells (hESCs), PS-NPs cause their immaturity and increase mitochondrial oxidative stress, and finally reduce the pluripotency of hESCs by activating the P38/Extracellular signal-regulated kinase (Erk) Mitogen-activated protein kinase (MAPK). It was also found that continuous exposure to PS-MPs reduces cardiac contractility and fetal blood flow [189].

The toxicity of MPs largely depends on their size and surface charge. A study has determined that NH2-labeled PS-NPs increase oxidative stress and toxicity in placental cells, inhibit protein kinase A activity, and cause cell cycle arrest in G1 or G2 phase [28]. Also, HTR-8/Svneo human trophoblast cells were used to measure the effect of 100 nm PS-NPs on placental trophoblasts at the mother-fetal interface. The results showed that these nanoparticles can reduce cell viability, stop the cell cycle, reduce the migration and invasion ability of cells, increase the intracellular ROS level, and produce TNF-α and IFN-γ pro-inflammatory cytokines in a dose-dependent manner, by entering the cytoplasm of trophoblast cells. In addition, RNA-sequencing results on HTR-8/Svneo cells showed the differential expression of 344 genes, which resulted in the activation of thyroid hormone, Hippo, TGF-β and FOXO signaling pathways [190]. NPs such as polycarbonate (PC), polyethylene terephthalate (PET), and PS, by inducing the highest toxicity, inhibit key placental enzymes and pose significant risks to the placenta [191]. In an in vitro study, the human ovarian granulosa COV434 cell line was exposed to different concentrations of NPs and it was found that COV434 cell line viability was significantly decreased at a concentration of 150 µg/ml. Also, the level of antioxidant markers SOD2 and GSH decreased, leading to oxidative stress [55]. Recently, extensive studies have been conducted on the role of MNPs with different sizes and doses on different human placenta cell lines (Table 3). These studies confirm the toxic effects of these polluting particles on the reproductive system and fertility of women. They confirm that MNPs particles can accumulate in the placenta and reduce the viability of its cells.

Table 3 Human cell cultures exposed to microplastics and assessment of their detrimental impacts

Conclusion

With the global increase in plastic consumption and human exposure to MNPs, attention has been drawn to the effect of these substances on the reproductive system and fertility in both sexes. Recent studies have confirmed the impact of these polluting particles on female infertility. MNPs can enter the body through various methods and affect its function by accumulating and changing the structure of the uterus, ovaries, and other components of the female reproductive system. These substances also affect the secretion and metabolism of sex hormones, disturb the balance of the reproductive endocrine system, and perturb the estrous cycle. Exposure to MNPs induces oxidative stress in the key components of the female reproductive system. It increases the risk of infertility in females by causing apoptosis in these cells and disrupting the ovulation process. Inflammation in the female reproductive system, which can lead to reproductive aging, is one of the main results of exposure to high amounts of MNPs. Also, they could trigger malignancies in the female reproductive system. In addition, MNPs have recently been found in human organs and tissues such as the placenta, which indicates their ability to cross the blood-placental barrier and transfer to fetal organs. MNP particles can show strong cytotoxic and genotoxic effects by passing through the placenta and accumulating in different tissues of the fetus and face serious problems in fetal growth and development. Also, maternal exposure to MNPs, in addition to intensifying disorders of the nervous system, immunity, and reproduction in offspring, may cause premature death and decrease the number of offspring. All these results show that MNPs as environmental pollutants have the potential to inflict irreversible harm on the reproductive system of females and the health of future generations and increase the rate of female infertility. Hence, managing microplastics to mitigate their risks and uphold reproductive health appears imperative. Addressing this concern entails implementing measures to diminish the prevalence of microplastics in the environment and to minimize human exposure to them.