Nicotinamide mononucleotide restores oxidative stress-related apoptosis of oocyte exposed to benzyl butyl phthalate in mice

Benzyl butyl phthalate (BBP) is a chemical softener and plasticizer commonly used in toys, food packaging, wallpaper, detergents and shampoos. The estrogenic actions of BBP have detrimental effects on humans and animals. In this study, the specific influence of BBP on mouse oocyte maturation was investigated using in vivo and in vitro models. The experiment first verified that BBP exposure significantly affected the rate of oocyte exclusion of the first polar body, although it did not affect germinal vesicle breakdown (GVBD) through in vitro oocyte culture system. Results of in vitro fertilization show that BBP exposure affects blastocyst rate. Subsequently, the results obtained by immunofluorescence staining technology showed that oocyte spindle organization, chromosomal arrangement and the distribution of cortical actin were disrupted by BBP exposure, and led to the failure of oocyte meiotic maturation and the subsequent early embryo development. Singe-cell transcriptome analysis found that BBP exposure altered the expression levels of 588 genes, most associated with mitochondria-related oxidative stress. Further analysis demonstrated that the detrimental effects of BBP involved the disruption of mitochondrial function and oxidative stress-induced early apoptosis. Nicotinamide mononucleotide (NMN) supplementation reduced the adverse effects of BBP. Collectively, these findings revealed a mechanism of BBP-induced toxicity on female reproduction and showed that NMN provides an effective treatment for BBP actions.

Automated summary

This study investigated the specific influence of benzyl butyl phthalate (BBP) on mouse oocyte maturation using in vivo and in vitro models. The results showed that BBP exposure significantly affected the rate of oocyte exclusion of the first polar body and blastocyst rate. Further analysis revealed that BBP disrupted mitochondrial function and induced oxidative stress-induced early apoptosis, while nicotinamide mononucleotide (NMN) supplementation reduced the adverse effects of BBP.