Propylparaben disrupts early embryonic development by causing oxidative stress-induced organelle dysfunction and actin zipper abnormality

Propylparaben (PrPB) is a commonly used preservative in personal care products and food items, but studies have shown that it can disrupt various physiological processes, especially in the reproductive system. Our previous research revealed the toxic effects of PrPB on mouse oocyte maturation. However, knowledge about the toxicity of PrPB in early embryos remains limited. In the present study, we demonstrated that in vitro exposure to 600 μM PrPB increased ROS levels, inducing autophagy, mitophagy and ER stress, ultimately leading to embryonic arrest at the 4-cell stage. PrPB exposure promoted autophagy through the induction of DNA damage, reflected by enhanced lysosome, LC3 and γH2A.X fluorescence signals. PrPB exposure enhanced mitophagy, as indicated by increased colocalization of mitochondria with LAMP1 and Parkin. PrPB exposure also caused ER stress, as indicated by disordered ER distribution and abnormal Ca²⁺ homeostasis. In addition, 600 μM PrPB exposure disrupted the formation of the actin zipper by interfering with the localization of ZO1 and E-cadherin, further affecting blastocyst formation. Although 300 μM PrPB exposure did not affect the embryo development rate, a decreased of the percentage of TE/total cell number and a increased of the percentage of ICM/total cell number was observed, indicating poor blastocyst quality. Taken together, the results of our study demonstrate that high-dose PrPB exposure causes oxidative stress-induced organelle dysfunction and abnormal actin zipper formation, whereas low-dose PrPB exposure affects early lineage specification.