Microplastics: Invisible to the eye but severely harmful to pregnancy and metabolic outcomes

In a recent study published in Ecotoxicology and Environmental Safety, researchers aimed to investigate the effects of polystyrene microplastics on pregnancy outcomes and glucose metabolism.

Study: Polystyrene microplastics disturb maternal glucose homeostasis and induce adverse pregnancy outcomes. Image Credit: Sansoen Saengsakaorat/Shutterstock.comStudy: Polystyrene microplastics disturb maternal glucose homeostasis and induce adverse pregnancy outcomes. Image Credit: Sansoen Saengsakaorat/Shutterstock.com

Background

For this, they developed a murine model system (C57BL/6J mice) and administered varying dosages of the microplastics during the gestation period.

To elucidate the underlying mechanisms and impacts of the pollutant on the model systems' health, they then carried out a host of analyses on the rodents, including histological-, blood cell-, biochemical-, quantitative real-time polymerase chain reaction, and immunohistochemistry assays.

Study findings revealed that polystyrene microplastics significantly disrupt glucose metabolism in pregnant mice. Furthermore, the pollutants were associated with an increased risk of insulin resistance in affected individuals, a crucial feature of gestational diabetes mellitus.

Alarmingly, higher dosages of the microplastics were found to destroy the structural integrity of the placenta, thereby resulting in intrauterine death.

Gestational diabetes and the adverse role of microplastics

Gestational diabetes mellitus (GDM) is a condition where an individual with no prior history of diabetes develops abnormally high blood sugar levels during pregnancy.

It is the most common pregnancy-associated complication and has been linked to undesirable clinical outcomes for both mothers and their unborn infants, a substantial portion of which are chronic and some of which may be life-threatening.

Given its prevalence and potential severity, the condition has been extensively studied, particularly in recent decades.

Researchers now know that GDM develops due to maternal beta cells being incapable of adapting to metabolic changes during pregnancy and is highlighted by varying degrees of insulin resistance (IR), giving rise to adverse outcomes, including preeclampsia, cesarean delivery, and gestational hypertension.

Unfortunately, the causes and risk factors associated with GDM remain obscure, with genetics, advancing maternal age, and environmental pollutants hypothesized to trigger or exacerbate the condition.

Microplastics (MPs) are minute plastic fragments generally smaller than 5 mm (and up to 1 μm) derived from several sources (microbeads used in the cosmetic industry, resin pellets that form plastic precursors, manufacturing runoff, and, most commonly, the environmental degradation of larger plastic objects).

Of the main types of MPs, polystyrene microplastics (PS-MPs) are the most prevalent and represent one of today's most ubiquitous anthropogenic environmental pollutants.

Several studies have highlighted the increased animal (including human) exposure to these pollutants, which are unknowingly ingested via oral, respiratory, and dermal routes.

A growing body of literature highlights the damage of these pollutants, particularly those smaller than 1.5 μm, on the organs of affected organisms.

Given their increased dependence on toiletries, ventilation, and packaged food and water – all known sources of PS-MPs – pregnant women may experience substantially higher exposure to these pollutants than the global mean.

Previous research has established the association between PS-MPs and IR in murine models. Given the crucial role of IR in GDM, this suggests that PS-MPs may result in significant adverse pregnancy outcomes via altered glucose metabolism. However, this phenomenon has hitherto never been formally investigated.

About the study

The present study aimed to investigate PS-MPs' impacts on mammalian glucose metabolism and clinical outcomes during pregnancy.

For this, 6- to 8-week-old female C57BL/6J mice (n = 28) were divided into four cohorts of differing exposure to 1 μm large MPs – Low MP (L-MPs; 0.1 mg/L), Medium MP (M-MPs; 1 mg/L), High MP (H-MPs; 10 mg/L), and controls (deionized water). Following the initiation of gestation, mice were exposed to their respective MP dosages for 18 days (Gestation Day [GD] 0.5 to GD 18.5) and then sacrificed.

To establish a baseline for the samples' blood glucose-regulating ability, mice were fasted on GD 10.5 and 15.5 and subjected to an oral glucose tolerance test (OGTT) on GD 11.5 and 16.5.

Samples of blood, pancreas, liver, placenta, and fetus were harvested post-sacrifice and subjected to organ coefficient weighing and downstream assays.

These included the hematological assay (conducted using an automated hemocyte analyzer), biochemical assays (including serum insulin levels), and histopathology assessments.

To elucidate the mechanisms of PS-MPs action, Periodic acid-Schiff (PAS) staining, Immunohistochemistry (IHC), and quantitative real-time polymerase chain reaction (RT-qPCR) were additionally carried out.

Study findings

Despite a gradual increase in sample water and food intake during pregnancy, mice in the H-MPs cohort display significantly lower mean body weights than in the other cohorts. Alarmingly, these trends were observed in H-MPs fetuses as well.

Histopathology assays revealed a substantial reduction in liver and placental weight across all exposure groups (compared to controls), elucidating substantial tissue damage caused by PS-MPs.

"As a multiparous animal, the reproductive toxicity of mice was evaluated from the rate of embryo absorption. All fetuses in the control group survived, and a high embryo resorption rate was recorded in the exposure groups. At GD18.5, the fetal body and tail length decreased compared with those of the control. These results suggested that PS-MPs could cause fetal growth restriction (FGR) and intrauterine death."

OGTT results revealed a gradual increase in glucose intolerance, most evident in the H-MPs cohort, despite no change in serum insulin levels.

Liver section analysis confirmed severe liver tissue damage in exposure cohort mice, with corresponding reductions in liver function. Finally, biochemical and RT-qPCR assays revealed extensive hepatic oxidative stress and the inhibition of insulin signaling pathways in exposure cohort mice.

Conclusions

PS-MPs exposure was found to substantially increase hepatic oxidative stress, activate inflammatory pathways, and inhibit insulin signaling pathways.

This, in turn, manifested IR and glycometabolic disorders in exposure cohort mice, resulting in severe weight loss, organ (particularly placenta and liver) damage, fetal growth restriction (FGR), and, in extreme cases, intrauterine death.

Alarmingly, the H-MPs cohort (10 mg/L) is representative of ambient environmental levels of PS-MPs, arguably an underestimation of human PS-MPs exposure during pregnancy.

This study, therefore, highlights the negative consequences of polystyrene and other microplastics on mammalian health and the need for immediate interventions against maternal pollutant exposure to improve maternal and fetal outcomes and prevent GDM and its comorbidities in these high-risk populations.

Journal reference:
Hugo Francisco de Souza

Written by

Hugo Francisco de Souza

Hugo Francisco de Souza is a scientific writer based in Bangalore, Karnataka, India. His academic passions lie in biogeography, evolutionary biology, and herpetology. He is currently pursuing his Ph.D. from the Centre for Ecological Sciences, Indian Institute of Science, where he studies the origins, dispersal, and speciation of wetland-associated snakes. Hugo has received, amongst others, the DST-INSPIRE fellowship for his doctoral research and the Gold Medal from Pondicherry University for academic excellence during his Masters. His research has been published in high-impact peer-reviewed journals, including PLOS Neglected Tropical Diseases and Systematic Biology. When not working or writing, Hugo can be found consuming copious amounts of anime and manga, composing and making music with his bass guitar, shredding trails on his MTB, playing video games (he prefers the term ‘gaming’), or tinkering with all things tech.

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