Melatonin alleviates the toxic effect of di(2-ethylhexyl) phthalate on oocyte quality resulting from CEBPB suppression during primordial follicle formation

• Published in: Journal of hazardous materials 2024-03, Vol.465, p.132997, Article 132997
• Main Authors: Wang, Jun-Jie, Zhang, Xiao-Yuan, Zeng, Yue, Liu, Qing-Chun, Feng, Xin-Lei, Yan, Jia-Mao, Li, Ming-Hao, Reiter, Russel J., Shen, Wei
• Format: Article
• Language: English
• Subjects: Di(2-ethylhexyl)phthalate; Melatonin; Oocyte; Primordial follicle; Single-cell transcriptome
• ISSN: 0304-3894; 1873-3336
• DOI: 10.1016/j.jhazmat.2023.132997

Presently, the exposure of plasticizers to humans and animals occurs daily, which pose a potential threat to reproductive health. In the present study, a pregnant mouse model exposed to di(2-ethylhexyl) phthalate (DEHP, one of the most common plasticizers) and melatonin was established, and the single-cell transcriptome technology was applied to investigate the effects of melatonin in ovarian cells against DEHP. Results showed that DEHP markedly altered the gene expression pattern of ovarian cells, and severely weakened the histone methylation modification of oocytes. The administration of melatonin recovered the expression of LHX8 and SOHLH1 proteins that essential for primordial follicle formation, and increased the expression of CEBPB, as well as key genes of histone methylation modification (such as Smyd3 and Kdm5a). In addition, the ovarian damage caused by DEHP was also relieved after the overexpression of CEBPB, which suggested melatonin could improve primordial follicle formation progress via enhancing CEBPB expression in mice. Besides, the apoptosis of ovarian cells induced by DEHP also was diminished by melatonin. The study provides evidence of melatonin preventing the damage mediated by plasticizers on the reproductive system in females and CEBPB may serve as a downstream target factor of melatonin in the process. [Display omitted] ●Melatonin recovered the progress of primordial follicle formation that impacted by DEHP in mice.●Melatonin greatly increased the expression of key histone methylation genes and CEBPB protein in oocytes.●The overexpression of CEBPB recovered the DEHP-mediated declining of histone methylation in oocyte.●Melatonin attenuated the toxicity of DEHP on oocyte through the histone methylation modification mediated by CEBPB.