The Surgical Pathologist’s (Potential) Role in Placental Microplastic Detection

In 2021, Ragusa et al¹  documented the first evidence of microplastic fragments, or microplastics (MPs), in 12 human placentas using Raman microspectroscopy. This biosensing technique characterizes biological structures based on size, shape, and composition.²  A year later, Ragusa et al³  used electron microscopy to find MPs located within the intracellular compartments of 10 normal, healthy term human placentas, inducing ultrastructural changes of mitochondria and endoplasmic reticulum (eg, narrowing and dilation, dysregulation of cytoplasmic ribosomes, lipid droplets). Recent murine models have also shown negative fetal outcomes when developing fetuses are exposed to these plastics in utero, such as growth restriction (up to 12% decrease in fetal weight)⁴  or placental dysfunction–induced fetal hypoxia with compensatory increases in umbilical artery blood flow (up to 43%; P < .01).⁵  Though no current studies (to our knowledge) have identified poor human fetal outcomes related to this exposure, it raises the question: should surgical pathologists start evaluating for the presence of MPs in placentas?

Given the paucity of literature on this topic, this editorial intends to introduce the surgical pathologist’s (potential) role in the matter. To do so, we will briefly describe: (1) what MPs are, (2) how MPs can affect placental health, (3) current findings of MPs in human placentas, and (4) what surgical pathologists may consider doing about this. Relevant peer-reviewed literature will be qualitatively reviewed and referenced where appropriate, and future research directions will also be introduced.

MPs (1 μm–5 mm), and their breakdown components, nanoplastics (NPs, 1 nm–1 μm), are small synthetic plastic particles resulting from environmental plastic waste degradation.⁶  Continued plastic pollution and poor plastic waste management practices, with rising plastic manufacturing, have resulted in a critical state of public health. According to Jung et al,⁷  an estimated 6300 million metric tons of plastic waste was present as of 2015, accumulating in approximately 79% of landfills or other natural environments. By 2050, plastic waste accumulation may rise to 12 000 million metric tons given continually rising poor waste management trends.⁷  MPs commonly enter humans through the gastrointestinal tract via contaminated food or water, which includes (but is not limited to) seafood, beer, tea, wine, soft drinks, fruit, vegetables, poultry, salt, sugar, and honey.⁸ 

This is problematic because M/NPs have been shown to (1) increase oxidative stress, (2) cause cytotoxicity, (3) disrupt endocrine and reproductive system regulation, (4) alter adipogenesis and energy production, and (5) induce inflammation, all through inappropriate activation of nuclear and cell receptors (eg, peroxisome proliferator–activated receptors α, β, and γ and retinoid X receptor).⁹  Though humans may not quite ingest an estimated credit card size worth (0.1–5 g) of M/NPs per week, as previously mentioned in academic literature and mainstream media,¹⁰  findings from Cox et al¹¹  suggest that humans may consume anywhere from 4000 to 121 000 particles annually depending on factors such as age, sex, water source, and inhalation while eating.

The placenta is a vital organ responsible for exchanging oxygen, blood, and other nutrients between a mother and fetus. Approximately 5 million pregnancies occur annually in the United States,¹²  though only 20% of placentas are estimated to be examined.¹³  In placentas, murine models show that M/NPs can (1) reduce amounts of glycogen-containing cells; (2) compromise uterine spiral artery function; (3) alter immune cell composition; (4) disturb the metabolism of amino acids, glucose, and cholesterol; and (5) disrupt complement/coagulation cascade pathways.¹⁴  In humans, pilot studies observing MP exposure in 2 sets of mother-infant pairs were led by Liu et al^15,16  with findings published in 2023. Infrared imaging spectrometry was used to identify 16 types of MPs (>74% ranging in size from 20 to 50 μm) in infant feces, breast milk, and infant formula in the first study.¹⁵  The authors of this study hypothesized that sources of MP exposure in mothers included scrub cleaner and toothpaste, and hypothesized sources in infants included breastfeeding, feeding bottles, and plastic toys.¹⁵ 

In the second study,¹⁶  the authors unveiled significant changes in placenta and meconium microbiota diversity (newer literature¹⁷  shows that first-pass meconium is not completely sterile, as was once believed) consequential to the ubiquitous presence of MPs, indicating that MP exposure affects infants in utero by way of mom and placenta. Additionally, 6.5 to 685 µg M/NPs per gram of tissue, with an average of approximately 126.8 µg/g, was recently found in 62 placentas using gas chromatography to mass spectrometry.¹⁸ 

Though future studies are needed to better determine the pathophysiologic impact of M/NPs in human placentas and fetuses, current literature supports that these ubiquitous and toxic microscopic plastic particles may be obesogens,¹⁹  and are likely found in many pregnant women. However, several limitations exist regarding the potential possibility of this practice. First, not all pathologists in every surgical pathology practice have the time or cost access to the laboratory tools mentioned herein. Second, there are no current gross or histologic documented findings in affected placentas to guide regular testing or classification. Third, the clinical relevance of M/NPs in human maternal-fetal cases is not clearly defined yet and needs to be further examined.

Recently, one author (C.P.S.) conducted a 7-day social media poll on X/Twitter²⁰  (Twitter, Inc) regarding surgical pathologists’ (potential) role in this matter (see Figure). Of 132 total responses (N = 132), 40.9% (n = 54 of 132) of respondents voted yes, and 39.4% (n = 52 of 132) of respondents voted no. An additional 19.7% (n = 26 of 132) voted maybe. There are multiple limitations of this poll, which include (but are not limited to) (1) the inability to definitively determine who the respondents are (ie, pathologists versus nonpathologists, as anyone on X/Twitter could respond to this poll), (2) no survey response percentage can be calculated, and (3) yes, no, and maybe are subjective responses without objective descriptions. Future in-depth studies targeting surgical pathologists’ opinions and practices on this matter should be pursued.

As M/NPs continue to become a public and environmental issue, though, perhaps placentas may be used to further quantify the status of plastic accumulation in humans, as suggested by a recent 15-year study from Hawaii.²¹  Also, many specific types of M/NPs that could be found in placentas are birefringent and may be visualized under polarized light microscopy (PLM).²²  Most surgical pathologists have polarizing tools that can be used with their light microscopes to visualize the presence of birefringent particles quite readily. Perhaps this could serve as an initial screening tool. However, the specificity of polarization for M/NP detection may be low, as prior studies have shown birefringence in placentas associated with labor-introduced foreign materials²³  or sequelae from infectious processes.²⁴  Also, pathologists in completely digitalized practices may not be able to use PLM, posing another limitation.

Currently, no PLM algorithms exist yet for M/NP detection in the placenta. But as we continue to learn more about these deleterious pathogens, histologic or PLM detection of these particles may be something that is investigated in the future, especially in cases of poor pregnancy or fetal outcome. In conclusion, M/NPs are a growing public and environmental health threat and are increasingly being identified in utero, hence the term plasticenta.^1,3  The possible negative outcomes in fetal health are too great to ignore. We hope this editorial sheds reasonable insight into the surgical pathologist’s potential role in further researching, and possibly one day detecting, these toxic particles, particularly in placental and perinatal pathology.