Biomaterial Database

Compartmentalized regulation of NAD+ by Di (2-ethyl-hexyl) phthalate induces DNA damage in placental trophoblast. 2022

Shuai Zhao, and Yun Hong, and Yue-Yue Liang, and Xiao-Lu Li, and Jiang-Chuan Shen, and Cong-Cong Sun, and Ling-Luo Chu, and Jie Hu, and Hua Wang, and De-Xiang Xu, and Shi-Chen Zhang, and Dou-Dou Xu, and Tao Xu, and Ling-Li Zhao

Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Department of Toxicology, Anhui Provincial Key Laboratory of Population Health and Aristogenics, MOE Key Laboratory of Population Health Across Life Cycle, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, China; School of Biology, Food and Environment, Hefei University, Hefei, 230601, China.

Di (2-ethyl-hexyl) phthalate (DEHP) is a wildly used plasticizer. Maternal exposure to DEHP during pregnancy blocks the placental cell cycle at the G2/M phase by reducing the efficiency of the DNA repair pathways and affects the health of offsprings. However, the mechanism by which DEHP inhibits the repair of DNA damage remains unclear. In this study, we demonstrated that DEHP inhibits DNA damage repair by reducing the activity of the DNA repair factor recruitment molecule PARP1. NAD+ and ATP are two substrates necessary for PARP1 activity. DEHP abated NAD+ in the nucleus by reducing the level of NAD+ synthase NMNAT1 and elevated NAD+ in the mitochondrial by promoting synthesis. Furthermore, DEHP destroyed the mitochondrial respiratory chain, affected the structure and quantity of mitochondria, and decreased ATP production. Therefore, DEHP inhibits PARP1 activity by reducing the amount of NAD+ and ATP, which hinders the DNA damage repair pathways. The supplement of NAD+ precursor NAM can partially rescue the DNA and mitochondria damage. It provides a new idea for the prevention of health problems of offsprings caused by DEHP injury to the placenta.