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Polystyrene Nanoplastics Disrupt Mouse Placenta Development in a Sex-Dependent Manner

Alahmadi, H.; Harbolic, A.; De Oliveria-Cordova, C.; Reynolds, R.; Jojy, M.; Potts, C.; Doan, S.; Mathur, T.; Islam, M. S.; Andrade, M. J.; Smith, Q.; Stapleton, P.; Mitra, S.; Warner, G. R.

2026-05-26 pharmacology and toxicology
10.64898/2026.05.22.727211 bioRxiv
Show abstract

Plastic production has been increasing exponentially. Throughout their lifespan, plastics degrade into smaller particles that accumulate in our bodies and the environment. Recent studies found these plastic particles can cross the placental barrier and reach the fetus. However, the impact of plastic particles on placental function is still unknown. We hypothesized that nanoplastics would disrupt placental growth and function, specifically focusing on transforming growth factor beta (TGF{beta}) signaling. To understand the impact of plastic particles on the placenta, we orally exposed pregnant CD-1 mice to 50 nm or 200 nm polystyrene plastic particles from gestation day 8 to day 15 at a human-relevant concentration of 5 mg/kg/day. After euthanization on day 15, placenta and fetus weights were recorded, and tissues were prepared for histomorphology and gene expression analysis. We observed a statistically significant decrease in the area of the decidua in the placentas for the 200 nm treatment group and a borderline significant decrease in decidua area for the 50 nm treatment group compared to control. However, when we separated by sex, only the male decidua were significantly decreased in the 200 nm group. Gene expression analysis of key signaling factors in the TGF{beta} pathway identified increased expression of Smad2 and Smad3, which may be suppressing prolactin and estrogen receptor signaling. Overall, both particle sizes disrupted placenta structure and signaling in a sex-dependent manner and may be acting as endocrine disruptors.

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