多环芳烃暴露致女性生殖毒性及其分子机制
Toxic effects and relevant molecular mechanisms of polycyclic aromatic hydrocarbon exposure on female reproductive health
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摘要:
多环芳烃（PAHs）是广泛存在的持久性环境毒物，其典型代表苯并a芘（BaP）是人类致癌物质，可通过胎盘屏障，最终代谢形成7，8-二氢二羟基-9，10-环氧化苯并a芘（BPDE）及其DNA加合物，直接影响女性生殖健康。本文从人群、动物、细胞和分子层次上阐述了PAHs对女性生殖健康的毒害作用和机制。在人群层次上，孕妇暴露于PAHs会导致流产、早产、胚胎停止发育等不良妊娠结局，并影响胎儿的正常生长发育。在动物水平上，BaP不仅会影响雌鼠的生殖健康，也会导致幼鼠生长发育不良。在细胞层次上，BaP或BPDE会抑制滋养层细胞的侵袭、迁移和增殖能力，促进滋养层细胞的凋亡、死亡。表观遗传学因素，例如DNA甲基化、miRNA、lncRNA，会直接参与导致细胞功能障碍的分子过程。目前该研究领域尚处于初级阶段，需要多学科合作，深入研究，为保障女性生殖健康提供科学依据和预防途径。
Abstract: Polycyclic aromatic hydrocarbons (PAHs) are widespread persistent environmental toxicants. Their typical representative benzoapyrene (BaP), a human carcinogen, can pass through the placental barrier and be finally metabolized into benzoapyrene-7, 8-dihydrodiol-9, 10-epoxide (BPDE) and its DNA adducts, directly affecting female reproductive health. This article reviewed the toxic effects and mechanisms of PAHs on female reproductive health at various levels such as populations, animals, cells, and molecules. At population level, exposure to PAHs in pregnant women could lead to adverse pregnancy outcomes such as abortion, premature delivery, and embryo undevelopment, and also affect the normal growth and development of fetuses. At animal level, BaP could not only affect the reproductive health of female rats, but also cause adverse developmental outcomes in young rats. At cellular level, BaP or BPDE could inhibit the invasion, migration, and proliferation of human trophoblastic cells, and promote the apoptosis and death of trophoblastic cells. Epigenetic factors, such as DNA methylation, miRNA, and lncRNA, are directly involved in the BaP exposure relevant molecular processes leading to cell dysfunction. At present, this research field is still in its primary stage, and requires multidisciplinary cooperation and in-depth studies, aiming to provide a scientific basis and preventive approach for female reproductive health protection.
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