增塑剂邻苯二甲酸二丁酯（DBP）广泛存在于人类生产和日常生活中，是目前公认的重要环境污染物。项目组前期研究发现孕期DBP暴露可导致子代（F1-F3代）生精障碍和睾丸支持细胞数量减少，采用多组学联合分析发现lncRNA-AABR06030998.1（DTSF1）可作为ceRNA参与miR-125-3p/Fstl3作用通路的调控而在该过程中发挥作用，但其作用机制尚不明确。本项目拟以前期构建的孕期DBP染毒传代效应大鼠为模型，探讨DTSF1/miR-125-3p/Fstl3作用通路在孕期DBP暴露致传代生精障碍中的作用；通过体外原代培养大鼠睾丸支持细胞实验，明确该作用通路关键因子的调控机制；通过整体动物干预实验进一步验证DTSF1在孕期DBP暴露致传代生精障碍中的作用。本项目的圆满实施可为有效减少DBP引起的传代生殖危害提供理论依据，为提高人口质量、促进人类生殖健康作出贡献。

Plasticizer dibutyl phthalate (DBP) is widely present in the human production and daily life, which is recognized as an important environmental pollutant. Our previous studies found that exposure of prenatal DBP during pregnancy can cause progeny (F1-F3 generation) impaired spermatogenesis and reduce the number of Sertoli cells. By combining multiple omics studies, it reveals that lncRNA-AABR06030998.1 (DBP-induced Transgenerational Spermatogenic Failure lncRNA 1, DTSF1) may act as ceRNA participant in the regulation of miR-125-3p/Fstl3 pathway, however mechanism is not clear. Based on our previous work, the project is planned to explore the role of DTSF1/miR-125-3p/Fstl3 pathway in transgenerational spermatogenesis disorders caused by prenatal DBP exposure. By taking advantage of the in vitro cultured rat primary Sertoli cells, we are aiming to investigate the regulation mechanism of the DTSF1/miR-125-3p/Fstl3 pathway. Furthermore, we intend to reveal the important role of DTSF1 in prenatal DBP exposure induced transgenerational spermatogenesis disorders via the in vivo experiments in rats. This project will provide theoretical basis for reducing the potential transgenerational harm to the offsprings of DBP exposure and make contributions to human reproductive health.