State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
Biol Reprod. 2022 Jul 25;107(1):349-357. doi: 10.1093/biolre/ioac092.
Triclosan is a broad-spectrum antibacterial agent and widely exists in environmental media and organisms. Triclosan exposure has been reported to have adverse effects on reproduction including embryo implantation disorder. During the embryo implantation window, it is vital that the endometrium develops into a receptive state under the influence of ovarian hormones. However, the effect of triclosan on embryo implantation and endometrial receptivity remains unclear. In the current study, we found a decreased embryo implantation rate, serum estrogen, and progesterone levels in mice exposed to triclosan from gestation days 0.5 to 5.5. Through RNA sequencing (RNA-seq), we identified nearly 800 differentially expressed genes, which were enriched in various pathways, including uterus development, inflammatory response, and immune system processes. Among those enriched pathways, the tight junction pathway is essential for the establishment of the receptive state of the endometrium. Then, genes involved in the tight junction pathway, including Cldn7, Cldn10, and Crb3, were validated by quantitative real-time polymerase chain reaction and the results were consistent with those from RNA-seq. Through immunofluorescence staining and western blotting, we confirmed that the tight junction protein levels of CLDN7 and CRB3 were increased. All these findings suggest that preimplantation triclosan exposure reduces the rate of embryo implantation through upregulating the expression of the tight junction genes and affecting the receptivity of the endometrium. Our data could be used to determine the sensitive time frame for triclosan exposure and offer a new strategy to prevent implantation failure.
三氯生是一种广谱抗菌剂,广泛存在于环境介质和生物体内。三氯生暴露已被报道对生殖系统产生不良影响,包括胚胎着床障碍。在胚胎着床窗口期,子宫内膜在卵巢激素的影响下发育为接受状态至关重要。然而,三氯生对胚胎着床和子宫内膜容受性的影响尚不清楚。在本研究中,我们发现暴露于三氯生(从妊娠第 0.5 天到第 5.5 天)的小鼠胚胎着床率、血清雌激素和孕激素水平降低。通过 RNA 测序(RNA-seq),我们鉴定出近 800 个差异表达基因,这些基因富集在各种途径中,包括子宫发育、炎症反应和免疫系统过程。在这些富集的途径中,紧密连接途径对于子宫内膜接受状态的建立至关重要。然后,通过定量实时聚合酶链反应验证了参与紧密连接途径的基因,包括 Cldn7、Cldn10 和 Crb3,结果与 RNA-seq 一致。通过免疫荧光染色和 Western blot 验证,我们证实了 CLDN7 和 CRB3 的紧密连接蛋白水平增加。所有这些发现表明,胚胎着床前暴露于三氯生通过上调紧密连接基因的表达并影响子宫内膜的容受性来降低胚胎着床率。我们的数据可用于确定三氯生暴露的敏感时间框架,并提供一种新的策略来预防着床失败。