Several studies investigated microplastic impacts on the reproductive system looking at the placenta as well as male testis and fertility.
In an article published on December 20, 2022, in the journal Metabolomics, Zahra Aghaei from the Memorial University of Newfoundland, Canada, and co-authors assessed the effects of microplastics exposure throughout gestation on placental metabolism. Normal functioning of the placental metabolism is key to providing the fetus with sufficient nutrients needed for its growth. The researchers exposed female mice directly after mating to three different concentrations of polystyrene (PS) microspheres of 5 µm reflecting those detected in human drinking water (102, 104, and 106 ng/L). After 17 days, they used 1H high-resolution magic angle spinning magnetic resonance spectroscopy (HRMAS MRS), multivariate analysis, and pathways analysis to evaluate metabolites in the placenta of mice.
While microplastics exposure did not affect maternal nor placental weights, the particles affected fetal weights in a dose-dependent manner with a 9% decrease of the group exposed to the highest concentration compared to unexposed control mice. Aghaei and co-authors identified 14 metabolites in the placenta of which two were significantly decreased in the mice exposed to 106 ng microplastics/L compared to the control. The relative concentrations of lysine and glycose decreased from 0.017 to 0.012 and from 0.082 to 0.059, respectively. Furthermore, the scientists reported that multivariate analysis showed “shifts in the metabolic profile with microplastics exposure and pathway analysis identified perturbations in the biotin metabolism, lysine degradation, and glycolysis/gluconeogenesis pathways.” The author pointed out several limitations of their study including that they did not analyze oxygen delivery to the fetus or microplastics other than those made of PS which might also have an impact on fetal growth. They concluded that microplastics exposure might potentially impact pregnancy outcomes so “efforts should be made to minimize exposure to plastics, particularly during pregnancy.”
Enzymes play a major role in metabolic as well as excretion functions. Christian Ebere Enyoh from the Saitama University, Japan, and co-authors were interested in the possible consequences of nanoplastics binding to placental enzymes. In the article published on December 17, 2022, in the Journal of Hazardous Materials, they described that they created in silico 3D molecular models of the ten most studied nanoplastic types. As molecular targets, the scientists downloaded models of six placental enzymes from the Protein Data Band, namely of the human soluble epoxide hydrolase, uracil phosphoribosyltransferase (UGT), human beta 1,3-glucuronyltransferase I (GST), human sulfotransferase (SULT), human N-acetyltransferase 2 (NAT) (ID: 2PFR), and human cytochrome P450 1A1(CYP). Nanoplastics were docked on specific binding pockets of these enzymes and binding affinities were retrieved. Besides these modulations, the researchers also performed density functional theory calculations for the nanoplastics and modeled their toxicity using a machine learning approach, i.e., artificial neural networks, as well as fractional factorial design.
The simulations showed that of the ten nanoplastic types, polycarbonate (PC), polyethylene terephthalate (PET), and PS had the highest binding affinity on the placental enzymes and, therefore, were the most toxic nanoplastic types. Enyoh and co-authors further reported that several nanoplastic types could generally act in an independent, synergistic and antagonistic manners when combined. While polymethyl methacrylate (PMMA), was found to have “the most significant antagonistic effect on the toxicity of the human enzyme receptors,” polyamide (PA) “showed a significant second-order synergetic effect on all enzymes” when combined with other nanoplastic types.
The authors emphasized that experimental studies are needed to validate their theoretical outcomes. Such studies should also consider the additives and other chemicals present in plastics which Enyoh et al. neglected in their simulation. Overall, their results would “suggest that nanoplastic mixture may pose significant risks to the placenta through inhibition of its key enzymes” which will subsequently not be able to metabolize other xenobiotics.
Microplastics have also been shown to induce reproductive toxicity in male organisms such as mice. In an article published on December 5, 2022, in the Journal of Hazardous Materials, Tianxin Zhao from the Guangzhou Medical University, Guangzhou, China, and co-authors explored the impact of PS microplastic exposure on offspring testis development and male reproductive health. The researchers exposed pregnant mice orally to 0.6 to 1 mg spherical microplastics of 0.5 µm in size per day starting from gestational day 1 until giving birth and their male offspring for another 70 days. Subsequently, testicular development and fertility of male offspring were determined on postnatal days 35 (prepubertal stage) and 70 (sexually mature stage).
Zhao and co-authors reported that microplastic exposure resulted in a disorder of testis development and spermatogenesis dysfunction on days 35 and 70, respectively. They also investigated the mechanisms behind the observed changes for which they measured serum sex steroids and cytokines, performed RNA sequencing and bioinformatics analysis. This showed that impaired testis development was related to reduced testosterone levels and antiandrogen receptor activity, inhibiting the cell cycle and the Hippo signaling pathways upon microplastic exposure. The Hippo signaling pathway controls organ size, e.g., through the regulation of cell proliferation. Spermatogenesis dysfunction was found to be mainly induced “through meiosis impairment and might be due to the imbalance of the spermatogenic immune microenvironment.” Overall, Zhao and co-authors concluded that “prenatal and postnatal exposure to PS microplastics resulted in testis development disorder and male subfertility.”
They emphasized that further research is required to elucidate the transgenerational effect. In a viewpoint article published on January 8, 2023, in the Journal of Agricultural and Food Chemistry, Jiaqi Sun from the University of Science and Technology, Beijing, China, and co-authors discussed that exposure of the paternal generation to small plastic particles might be inherited to the offspring, e.g. by epigenetic mechanisms. Thereby, the authors mainly highlighted that future studies are needed to elucidate the multigenerational effects of micro- and nanoplastic since these are currently overlooked. Hereby, the focus should not only be on the genetic effect on the offspring of the first and second but also the third and fourth generations.
References
Aghaei, Z. et al. (2022). “Maternal exposure to polystyrene microplastics alters placental metabolism in mice.” Metabolomics. DOI: 10.1007/s11306-022-01967-8
Enyoh, C. E. et al. (2022). “Evaluation of nanoplastics toxicity to the human placenta in systems.” Journal of Hazardous Materials. DOI: 10.1016/j.jhazmat.2022.130600
Sun, J. et al. (2022). “Paternal Inheritance Is an Important, but Overlooked, Factor Affecting the Adverse Effects of Microplastics and Nanoplastics on Subsequent Generations.” Journal of Agricultural and Food Chemistry. DOI: /10.1021/acs.jafc.2c08408
Zhao, T. et al. (2022). “Prenatal and postnatal exposure to polystyrene microplastics induces testis developmental disorder and affects male fertility in mice.” Journal of Hazardous Materials. DOI: 10.1016/j.jhazmat.2022.130544
This article was originally published by Lisa Zimmermann at the Food Packaging Forum.
