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.

邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种广泛使用的增塑剂。母亲在怀孕期间接触 DEHP 会降低 DNA 修复途径的效率，从而阻碍 G2/M 期的胎盘细胞周期，并影响后代的健康。然而，DEHP抑制DNA损伤修复的机制仍不清楚。在这项研究中，我们证明 DEHP 通过降低 DNA 修复因子招募分子 PARP1 的活性来抑制 DNA 损伤修复。NAD ⁺和 ATP 是 PARP1 活性必需的两种底物。DEHP通过降低 NAD ⁺合酶 NMNAT1的水平来减少细胞核中的 NAD + ，并通过促进合成来提高线粒体中的^{NAD + 。}此外，DEHP破坏线粒体呼吸链，影响线粒体的结构和数量，并减少ATP的产生。^{因此，DEHP通过减少NAD +}和ATP的量来抑制PARP1活性，从而阻碍DNA损伤修复途径。补充NAD ⁺前体NAM可以部分挽救DNA和线粒体的损​​伤。为预防DEHP对胎盘损伤引起的后代健康问题提供了新思路。