Polystyrene Microplastics Induced Ovarian Toxicity in Juvenile Rats Associated with Oxidative Stress and Activation of the PERK-eIF2α-ATF4-CHOP Signaling Pathway

Abstract

Numerous reports confirm that microplastics exposure could induce reproductive toxicity in mammals. However, the effects of microplastics exposure during juveniles on ovarian apoptosis through oxidative and endoplasmic reticulum (ER) stresses remains unclear, which is the focus of our study. In the present study, female rats (4 weeks old) were exposed to polystyrene microplastics (PS-MPs, 1 μm) at different dosages (0, 0.5, and 2.0 mg/kg) for 28 days. Findings revealed that 2.0 mg/kg of PS-MPs distinctly increased the atretic follicle ratio in the ovary and dramatically reduced the serum levels of estrogen and progesterone. Additionally, the oxidative stress indicators declined, including the activity of superoxide dismutase and catalase, whereas the malondialdehyde content in the ovary was considerably enhanced in the 2.0 mg/kg PS-MPs group. Furthermore, the expressions of genes related to ER stress (PERK, eIF2α, ATF4, and CHOP) and apoptosis were remarkably elevated in the 2.0 mg/kg PS-MPs group compared with those in the control group. We found that PS-MPs induced oxidative stress and activated the PERK-eIF2α-ATF4-CHOP signaling pathway in juvenile rats. Moreover, with the oxidative stress inhibitor N-acetyl-cysteine and eIF2α dephosphorylation blocker Salubrinal treatment, ovarian damage induced by PS-MPs was repaired and associated enzyme activities were improved. Overall, our results indicated that PS-MPs exposure induced ovarian injury associated with oxidative stress and activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in juvenile rats, providing new prospects for assessing the health risks of children exposed to microplastics.

Microplastics and Oxidative Stress—Current Problems and Prospects

“…Polystyrene was the polymer that was most frequently used in studies on how MPs affected RS stress [145,[148][149][150]. Rats, mice, and fish were used in these analyses [145,[148][149][150].…”

“…Polystyrene was the polymer that was most frequently used in studies on how MPs affected RS stress [145,[148][149][150]. Rats, mice, and fish were used in these analyses [145,[148][149][150]. It was discovered that PS (1 µm, 2.0 mg/kg) caused young rats to express genes linked to ER stress (PERK, eIF2α, ATF4, and CHOP) [150].…”

“…Rats, mice, and fish were used in these analyses [145,[148][149][150]. It was discovered that PS (1 µm, 2.0 mg/kg) caused young rats to express genes linked to ER stress (PERK, eIF2α, ATF4, and CHOP) [150]. The stress of ER and oxidative damage were discovered to cause nephrotoxicity in other trials carried out on rats using the same kind of particle (PS, 1 µm, 2.0 mg/kg/d) [148].…”

Microplastics and Nano-plastics Contamination in Foods: Current Understanding of the Health Impact on Human and Potential Solutions

“…Studies have found that MPs can cause reproductive harm in animals [168,169]. 2.0 mg/kg of polystyrene microplastics (PS-MPs) significantly raised the atretic follicle ratio in the ovary and significantly decreased blood levels of estrogen and progesterone [168].…”

“…Studies have found that MPs can cause reproductive harm in animals [168,169]. 2.0 mg/kg of polystyrene microplastics (PS-MPs) significantly raised the atretic follicle ratio in the ovary and significantly decreased blood levels of estrogen and progesterone [168]. Furthermore, the activity of oxidative stress markers such as superoxide dismutase and catalase were significantly decreased [168], indicating that PS-MPs exposure could induce ovarian injury associated with oxidative stress.…”