A review of the impact of micro‐ and nanoplastics on female reproduction: What we know and gaps in knowledge

Abstract

Micro‐and nanoplastics (MNPs) are breakdown products of plastics, and humans are exposed to these particles through air, water, food, and soil. There is a growing concern that human exposure to MNPs negatively impacts health. In this review we will discuss the potential health impact of MNPs on ovarian function and the hypothalamic–pituitary‐ovarian (HPO) axis. We will highlight that the deleterious effects of MNPs on female reproductive health have been mostly documented in animal models. Studies have demonstrated that MNPs accumulate in ovarian tissue, disrupt hormonal signaling, and induce oxidative stress, leading to hormonal irregularities, ovarian atrophy, and increased androgen levels. Additionally, there is accumulating evidence that not only are MNPs a concern by themselves, but they are also carriers of endocrine‐disrupting chemicals (EDCs) which further exacerbate reproductive dysfunction. While animal models demonstrate reproductive toxicity from MNP exposure, there are gaps in our knowledge on whether these findings can be translated to humans. Human clinical trials to directly determine the impact of MNPs are unethical because the evidence suggests MNP exposure may be detrimental to health. In this review, we highlight gaps in our knowledge and suggest areas which need further research.

1. INTRODUCTION

1.1. Background and significance

Plastics have contributed to advancements across industries due to their low cost and versatility, but their increasing production raises environmental and health concerns. Micro‐ and nanoplastics (MNPs), are defined as tiny plastic particles ranging from microplastics (100 nm–5 mm) to nanoplastics (less than 100 nm), which are generated through use, aging, and various fragmentation processes. ¹ MNPs then enter the human body through inhalation, ingestion, and dermal contact. MNPs come in a variety of sizes, shapes (spheres, fibers, and fragments), properties (lipophilic or hydrophobic), and chemical compositions, thereby affecting their transportation, distribution, absorption, and impact. ² During the processing and development of plastics, there are often additives included to alter the shape, structure, durability, and thickness of the plastic. Some of these plastic constituents are and/or can be endocrine‐disrupting chemicals (EDCs), such as phthalates, organophosphate esters, and bisphenols, heavy metals (chromium, lead, and cadmium), and microorganisms. Research in animal models has demonstrated MNPs can negatively affect the reproductive and endocrine systems and can cause reductions in fertility. Basic science data suggest MNP exposure may impact ovarian steroidogenesis and folliculogenesis. ³ , ⁴ EDCs, carried by MNPs, studied in model organisms also affect the synthesis, secretion, and elimination of hormones that are vital for normal endocrine and reproductive functions. ⁵ The growing list of toxic effects of MNPs has generated an urgent need to understand their impact on human health, particularly on the female reproductive system.

While the presence of MNPs in human follicular fluid has been recently confirmed, there are still gaps in our knowledge as to the direct human health impact of MNP exposure. This review synthesizes information derived from animal studies and incorporates, where possible, what is known in humans. In developing this review, our goal is to raise awareness as to the potential health impact MNPs may have and to highlight what future/further research is needed.

2. MATERIALS AND METHODS

This narrative review was conducted in accordance with the scale for the assessment of narrative review articles (SANRA) guidelines to ensure methodological rigor and reporting quality. A comprehensive literature review was conducted using PubMed and Google Scholar, capturing all available studies relevant to the topic. The resulting reference set comprised publications dated between January 1, 2018, and March 1, 2025. Search terms included combinations of the following: microplastics, nanoplastics, female reproductive system, ovarian function, hypothalamic–pituitary‐ovarian axis, endocrine disruption, fertility, folliculogenesis, and steroidogenesis. Priority was given to research examining the specific cellular impacts of MNPs and EDCs on the ovary and HPO axis in animals including mice, zebra fish, and rats, cell culture, and human studies.

2.1. Inclusion criteria

Original studies (in vivo rat, mice, and zebrafish studies, in vitro experiments, and human studies), studies reporting cellular, molecular, or systemic effects of MNPs and/or EDCs on female reproductive tissues or hormones, and studies published in English.

2.2. Exclusion criteria

Studies unrelated to female reproductive health, editorials, and conference abstracts without primary data. Studies were excluded if they lacked a clear methodology (defined as insufficient detail regarding study design, participant selection, data collection, or analysis procedures), or if they lacked clear results (defined as the absence of specific quantitative findings or identifiable qualitative themes that support the study's conclusions).

2.3. Data extraction and synthesis

Titles and abstracts were screened for relevance. Full‐text articles meeting inclusion criteria were reviewed. Data were extracted regarding study model (human, animal, in vitro), MNP type and exposure route, targeted reproductive components (e.g., ovary, HPO axis), and molecular pathways affected. Results were organized thematically and tables were constructed to summarize the findings.

2.4. Limitations

This review primarily synthesizes preclinical (animal, in vivo, and in vitro) data. We highlight what has been found in the preclinical studies as well as what has been translated to humans. We end the review by highlighting gaps in knowledge and needed future research/exploration. Caution was taken to avoid over‐extrapolation, and limitations of the current evidence base are discussed.

3. RESULTS

3.1. Preclinical and clinical data discussing the potential impact of MNPs/EDCs on the hypothalamic–pituitary‐ovarian (HPO) axis and ovarian function

Review of human reproductive physiology

The human female reproductive system is comprised of the hypothalamus‐pituitary, ovaries, fallopian tubes, uterus, cervix, and vagina, which work together to perform various biological processes, from menstruation to pregnancy and childbirth. The hypothalamic–pituitary‐ovarian (HPO) axis is critical to the balance and functioning of the female reproductive system.

The HPO axis should be viewed as a concerted system that allows for the cyclic generation of gonadotropic and steroid hormones. The release of gonadotropin‐releasing hormone (GnRH) from the hypothalamus stimulates the pituitary gland to produce follicle‐stimulating hormone (FSH) and luteinizing hormone (LH), which are critical for ovulation. The ovaries are the final component of the HPO axis, and intact ovarian function is critical to ensure the proper growth and implantation of primary follicles, which are precursors to embryonal development. ⁶ There are three cell types within the ovaries: stromal cells, granulosa cells, and theca cells. Stromal cells provide a structural framework for the ovary and support oogenesis. Theca cells synthesize androgens, and granulosa cells convert androgens into estrogen and progesterone.

The ovaries respond to FSH and LH from the pituitary to produce estrogen and progesterone at fluctuating concentrations throughout the menstrual cycle, which are necessary for follicle maturation, ovulation, and corpus luteum formation. They also provide negative feedback to the HPO axis. ⁷ These processes allow for the development of a follicle (egg) every month for ovulation, while priming the uterine endometrium for embryo implantation. This cycle allows for either fertilization (and subsequent development of the zygote) or menstruation (failed fertilization). If proper regulation of ovulation does not occur, the menstrual/reproductive cycle may become irregular, resulting in dysfunctions, such as polycystic ovarian syndrome (PCOS), amenorrhea, and infertility. The aim of this article is to provide a review of recent literature on the varied effects of MNP exposure on ovarian function and the HPO axis in order to direct policy and health guidelines regarding the consumption of plastics.

Review of human and rodent ovarian function

Ovarian folliculogenesis is a complex biological process involving the growth and maturation of ovarian follicles, and is essential for female reproduction. This process is regulated by various factors including mechanical signals from theca cells, hormonal influences, and microRNA activity. Only 0.1% of the follicles reach the pre‐ovulation stage; therefore, this process is also incredibly selective.

MNPs have been shown to interfere with folliculogenesis in mouse studies. ⁸ , ⁹ , ¹⁰ In these models, rodents were typically exposed to polystyrene microplastics (PS‐MPs) via oral gavage or ingestion in drinking water, mimicking environmental exposure routes. Following repeated exposure across estrous cycles, researchers found MNP accumulation within ovarian compartments, including the follicles and corpus luteum. While direct evidence of MNPs in rodent follicular fluid is limited, their detection in these compartments strongly suggests systemic circulation can deliver particles to the ovary. Mechanistically, MNPs appear to interfere with follicular development by disrupting hormonal signaling, inducing oxidative stress, and damaging granulosa cells, ultimately leading to decreased antral follicles and increased atretic follicles. ³ , ⁴ , ¹⁰ , ¹¹ Importantly, microplastics have recently been detected in human ovarian follicular fluid, but whether the mechanistic effects observed in animal models apply directly to human reproductive physiology remains unknown. ¹²

In humans, a recent study confirmed the presence of MNPs in the follicular fluid of 18 women undergoing IVF, marking the first clinical evidence of such exposure. ¹² Although mechanistic data in humans remain limited, the detection of MNPs in follicular fluid indicates that these particles can cross the blood‐follicle barrier and accumulate in the ovarian microenvironment. This supports the hypothesis that the ovary is a potential target for systemic MNP exposure, although further studies are needed to determine whether this accumulation affects oocyte quality, hormonal balance, or fertility outcomes.

Controlled trials on humans are unethical, so researchers used mouse models for further study. They exposed mouse oocytes in vitro to seven types of fluorescence‐labeled MP beads: polyethylene (PE), polyvinyl chloride (PVC), polypropylene (PP), polystyrene (PS), chlorinated polyethylene (CPE), polymethylmethacrylate (PMMA), and polytetrafluoroethylene (PTFE). These polymers were selected based on their detection in human follicular fluid samples. The study found that smaller MNPs, such as 50 nm PE particles, were able to penetrate the zona pellucida and enter oocytes, potentially causing intracellular damage. In contrast, larger particles like 500 nm PMMA remained adhered to the zona pellucida, forming a physical barrier that may disrupt communication between the oocyte and surrounding follicular fluid, thereby impairing oocyte maturation.

Similarly, an in vivo study that orally administered 5 μm polystyrene microplastics (PS‐MPs) to rats for four estrous cycles found that PS‐MPs accumulated in various compartments of the ovarian tissue, including follicles, corpus luteum, and stroma. ³ Notably, higher concentrations of PS‐MPs were detected in luteal and theca cells, likely because of their proximity to blood capillaries, suggesting that MNPs may be transported to the ovary via the circulatory system after crossing the intestinal barrier. ⁴ This accumulation was associated with a reduction in relative ovarian weight, altered estrous cycle duration, reduced serum estradiol concentration, and changes in folliculogenesis demonstrated by a decrease in the number of tertiary follicles and an increase in atretic and cystic follicles. ⁴

Studies in animal models also suggest that microplastics can cause ovarian atrophy and disrupt the structural integrity of ovarian tissues, which is essential for healthy follicle development. ¹³ Microplastics can also impair folliculogenesis in mammals by causing ovarian cysts, reduced follicular growth, and granulosa cell death. ¹³ These effects are linked to oxidative stress, inflammation, and disruption of hormonal regulation, ultimately affecting reproductive health in animal models. ³ , ⁴ , ¹¹ , ¹³

More specifically, in a study conducted on female mice, PS‐MPs were found to accumulate in ovaries after continuous exposure for 35 days. ¹⁰ This study noted that, while the number of primordial, primary, and secondary follicles remained unchanged, there was a significant decrease in the number of antral follicles in the PS‐MPs treated ovaries compared to the control group. These findings provide an important area for future research to determine if MNPs also impact these same cells. In humans, antral follicles contain immature eggs and are an indication of a woman's ovarian reserve or the number of eggs left in her ovaries. These data may suggest in women, MNP exposure may be linked to reductions in fertility due to a reduction in egg production, but further research is needed to make this association. One potential mechanism by which the MNPs may influence in the ovary is through activation of interleukin‐6 (IL‐6), a proinflammatory factor which was elevated in the mice following exposure to the MNPs when compared to the control group. ¹⁰

Additionally, there are other data suggesting that, in rodents, microplastics may disrupt the expression of cytoskeletal proteins in the ovary, affecting oocyte maturation and cell division, which would then impact folliculogenesis. Studies have demonstrated a decrease in the expression of α‐tubulin and disheveled‐associated activator of morphogenesis (DAAM‐1) in rat ovaries exposed to PS‐MPs, highlighting an additional potential mechanism through which microplastics could contribute to female infertility, ³ because alterations in DAAM‐1 expression can disrupt Wnt signaling, potentially contributing to the observed defects in folliculogenesis and steroidogenesis. Notably, other studies have shown that PS‐MPs can induce pyroptosis– a type of programmed cell death induced by inflammation and involving reactive oxygen species (ROS)– and apoptosis of ovarian granulosa cells, further contributing to ovarian dysfunction. ⁴ It will be important to determine if these same effects are happening in humans following MNP exposure.

Another recent study using samples taken from 19 infertile women found the presence of MNPs in human follicular fluid (hFF). ¹⁴ In this study, MNPs were stratified in several dimensions, such as diameter and MNP concentration. Their detection in hFF highlights the need for further research to determine whether the mechanistic effects observed in animal models translates to human reproductive physiology. The preclinical results are summarized in Table 1.

TABLE 1.

Summary of MNP effects on the female reproductive system.

Study	Model	Key findings	Proposed mechanisms
Dou et al. (2024) 9	Mice	Increased testosterone, PCOS‐like changes, delayed puberty	Cyp17a1 upregulation, increased androgen production
Liu et al. (2022) 10	Mice	Ovarian accumulation of PS‐MPs, reduced antral follicles	IL‐6 mediated inflammation
Montano et al. (2025) 12	Humans (n = 18)	MNPs detected in human follicular fluid	Penetration of blood‐ovarian barrier (clinical impact unclear)
Ni et al. (2025) 14	Humans (n = 19), mouse oocytes	MNPs stratified by size/type; smaller MNPs entered oocytes	Physical interference with oocyte maturation
Haddadi et al. (2022) 3	Rats	Accumulation in ovarian tissue, altered estrous cycles	Disrupted folliculogenesis
Hou et al. (2021) 4	Rats	Reduced estradiol, granulosa cell death	Wnt signaling disruption, oxidative stress
Zheng et al. (2023) 15	Zebrafish	Decreased estradiol‐to‐testosterone ratio	3βHSD and 17βHSD enzyme disruption
Gupta et al. (2023) 16	Zebrafish	Disrupted steroidogenesis	Enzymatic disruption affecting sex hormones
Wang et al. (2023) 17	Mice	Decreased estrogen/progesterone later in life	Hormonal imbalance via multiple pathways

Abbreviations: 3βHSD, 3β‐hydroxysteroid dehydrogenase; 17βHSD, 17β‐hydroxysteroid dehydrogenase; DAAM‐1, disheveled‐associated activator of morphogenesis‐1; hFF, human follicular fluid; IL‐6, interleukin‐6; MNPs, micro‐ and nanoplastics; MPs, microplastics; PCOS, polycystic ovary syndrome; PS‐MPs, polystyrene microplastics.

Impact on steroidogenesis

Steroidogenesis is another key component of ovarian function, and it is a complex process involving the conversion of cholesterol into sex steroids and is primarily regulated by granulosa and theca cells. ¹⁵ During ovarian steroidogenesis, theca cells are the site of the multistep conversion of cholesterol into testosterone. Neighboring granulosa cells utilize the enzyme aromatase to convert testosterone to estradiol. A 2023 study found that exposure to microplastics significantly decreased the estradiol to testosterone ratio in zebrafish models. ¹⁶ More specifically, this paper suggests exposure to MNPs increased the activity of 3β hydroxysteroid dehydrogenase (3βHSD) and decreased the activity of 17β hydroxysteroid dehydrogenase (17βHSD) which altered the hormonal homeostasis and gene expression related to the HPG axis. While this study focuses on an aquatic model, the enzymes 3βHSD and 17βHSD also play roles in human steroidogenesis, so determining if human exposure to MNP may also impact steroidogenesis is a gap in our current knowledge.

Ovarian and hormonal changes leading to PCOS‐like effects

Likewise, mice exposed to MNPs during lactation were found to have increased levels of testosterone in adulthood which resulted in thickening of the theca cell layer. ⁹ This study also found that the mechanism of increased testosterone levels in mice exposed to PS‐MPs stemmed from a significant upregulation in the expression of Cyp17a1, a pivotal enzyme which influences androgen production in both mice and humans. ⁹ In the above mentioned study in mice, those which were exposed to MNPs through lactation had delayed puberty and exhibited PCOS‐like (PCOS is a female endocrine condition marked by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries) ovarian function in later life due to increased testosterone levels. Other studies in mice have found that early MP exposure can lead to decreased serum estrogen and progesterone levels later in life. ¹⁷ Taken in combination, data from preclinical studies suggest MNPs can cause ovarian atrophy, hormonal imbalance, and granulosa cell pyroptosis through oxidative stress and disrupted signaling pathways. The association between these ovarian and hormone changes with MNPs is well documented in mammals and is a reason for further caution related to MNP use and ingestion by humans. Cyp19b is an essential gene which converts various androgens to estrogens—essential for many of the female sexual characteristics. A study showed that varying the bisphenol A (BPA) concentration in zebrafish models led to a non‐monotonic (U‐shaped) change in Cyp19b expression at varying BPA concentrations, indicating that this EDC disrupted the Cyp19b powered steroidogenesis pathway. ¹⁸ This disturbance in the estrogen signaling pathway causes deregulation of gonadotropic hormones and subsequent degeneration of gonadotropic cells, leading to future endocrine problems, such as PCOS and ovarian inflammation.

Studies in rat models have also shown that BPA exposure leads to an increased release of FSH and LH from the pituitary gland, with the effect being more pronounced on LH than on FSH, a pattern characteristic of PCOS. ¹⁹ Another toxic effect of MNPs is their ability to induce insulin resistance. A study in a mouse model exposed to nanoplastics demonstrated a notable elevation in blood glucose levels, glucose intolerance, and oxidative stress, ultimately culminating in insulin resistance through modification of glycogen storage. ²⁰ Another study in mouse models demonstrated complete insulin resistance, weight loss, elevated blood glucose levels, and systemic inflammatory symptoms in mice exposed to MNPs through upregulation of the insulin receptor gene, while decreasing the insulin receptor substrate. ²¹

The animal studies, summarized in Table 2, revealed that MNPs and EDCs can lead to PCOS‐like effects and insulin resistance. These preclinical findings linking MNP exposure to a PCOS‐like condition are concerning, especially since there has been a rise in the diagnosis of PCOS, which parallels the increased presence of MNP exposure. The relationship between MNPs, diabetes, and metabolic syndrome is an area for further research.

TABLE 2.

Summary of endocrine disrupting chemicals effects on the female reproductive system.

Source	Animal/model	Target cells	Finding	Mechanism
Molina et al. (2018) 18	Female zebrafish (Danio rerio)	Gonadotroph cells	BPA exposure leads to changes in the Cyp19b transcripts	Deregulation of gonadotropic hormones causing degeneration of gonadotropic cells
Wang et al. (2023) 17	Mice	Liver and pancreatic cells	Significant increase in blood glucose, glucose intolerance and insulin resistance	Exposure leads to decreased phosphorylation of AKT and GSK3β attenuating the increase in fasting blood glucose levels and insulin resistance
Yang et al. (2024) 21	Mouse	Mainly Hepatic, renal cells	Weight loss, hyperglycemia, decreased triglycerides, and insulin resistance	Decrease in the levels of insulin receptor substrate 1 (IRS1) mRNA and upregulation of INSR gene

Abbreviations: AKT, AKT serine/threonine kinase; BPA, bisphenol A; Cyp19b, cytochrome P450, family 19, subfamily A, polypeptide 1b; GSK3β, glycogen synthase kinase 3 beta; INSR, insulin receptor; IRS1, insulin receptor substrate 1.

Disruption of the HPO axis, accumulation in progeny and other implications

As previously introduced, the human female HPO axis is a coordinated cascade that releases hormones and aids in the working of the female reproductive system. The functioning of the HPO axis is particularly sensitive to endogenous hormonal changes, owing to its tight regulation. EDCs have been found to alter the function of the HPO axis, leading to anovulation, subfertility, and infertility in animal models. ¹⁸ Some research suggests that MNPs act as “molecular sponges,” which concentrate EDCs at levels higher than those typically found in nature. ²²

Similarly, a study demonstrated that indirect MNP exposure via the food chain led to their accumulation in mouse embryos. ²³ While this suggests MNPs can cross the placental barrier in mice, the specific transfer efficiency and the implications for human placental transfer, which differs significantly in structure and function, require further investigation. The mice progeny exposed to MNPs during pregnancy and lactation have also been shown to have lower birth and postnatal bodyweight. ²⁴ Similarly, progeny of mice exposed to MNPs during gestation and lactation exhibited reduced birth and postnatal bodyweight. ²⁴ A key limitation of current animal research is the challenge of extrapolating these observed effects and doses to environmentally relevant human exposure scenarios. Likewise, beyond single‐contaminant exposures, studies have begun to explore the complex interactions of MNPs with other environmental pollutants. For instance, co‐exposure to MNPs and various plastic additives has demonstrated significant phenotypic toxicity in zebrafish embryos. Notably, this study observed developmental malformations even at concentrations where individual contaminants alone showed no apparent toxicity, suggesting potential synergistic or additive effects with pollutants such as bisphenol S and phthalates. ²⁵

4. DISCUSSION

Plastics have advanced many aspects of human life; however, there is accumulating evidence that its breakdown into MNPs and the further release of the EDCs from the MNPs may have negative impacts. Data now suggest there are concerns regarding their potential adverse impacts on ecological systems, human health, and economic stability, particularly focusing on MNPs.

4.1. Strengths and limitations

The current body of research, as synthesized in this review, demonstrates gaps in our knowledge. The use of controlled in vitro and animal models has been instrumental in identifying potential biological mechanisms by which MNPs may exert reproductive toxicity, such as oxidative stress and inflammatory responses, but we do not currently have these data in humans. The benefit of the preclinical studies is that these are controlled experiments where the researchers have the ability to control for all aspects of MNP exposure—conditions which are lacking/impossible in human studies which provides a limitation. Despite the inability to directly translate preclinical studies to humans based on the inability to ethically and knowingly expose humans to MNPs for testing their health impact, the existing data are particularly concerning and indicate the need to determine the potential health impact of MNPs in humans. Animal models often employ MNP concentrations and exposure routes (e.g., high‐dose gavage, direct injection) that may not accurately reflect environmentally relevant human exposures. Interspecies differences in physiology, metabolism, and reproductive biology also limit the direct translatability of findings from model organisms to humans. Animal models have provided initial insights into the potential for impact of MNPs and potential health outcomes, though it is crucial to interpret these findings with consideration for species‐specific differences and experimental conditions.

5. CONCLUSION

This narrative review highlights current data from in vivo and in vitro studies examining the impact of MNPs on female reproductive health. Our findings are summarized in Figure 1. While preclinical models have identified mechanisms such as oxidative stress and inflammation, human data are lacking. Animal studies, though informative, often rely on high‐dose exposures and routes not reflective of typical human contact, and physiological differences limit their direct applicability. Despite these limitations, significant progress has been made in elucidating potential toxic effects of MNPs to the female reproductive system(s). As environmental MNP exposure continues to rise, addressing the translational gap between preclinical findings and human health outcomes is critical for guiding future research, informing public health initiatives, and shaping environmental policy to mitigate reproductive risks.

FIGURE 1.

Diagrammatic algorithm of micro‐ and nanoplastic (MNP) effects, mechanisms of action, emerging human evidence, and knowledge gaps.

AUTHOR CONTRIBUTIONS

Sanchayana Raghuvir: Conception and design, planning, data acquisition and analysis and manuscript writing. Shawn Alex: Design, planning, data acquisition and analysis and manuscript writing. Deborah Clegg: Supervision, writing‐reviewing and editing.

CONFLICT OF INTEREST STATEMENT

The authors have no conflicts of interest.

DATA AVAILABILITY STATEMENT

Data sharing is not applicable to this article as no new data were created or analyzed in this study.