C.S Mott Center for Human Growth and Development, Wayne State University, Detroit, MI, USA.
Institute of Reproductive Health, Center for Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
Placenta. 2024 Sep 26;155:88-99. doi: 10.1016/j.placenta.2024.07.315. Epub 2024 Aug 10.
Embryo implantation is a tightly regulated process, critical for a successful pregnancy. After attachment of the blastocyst to the surface epithelium of the endometrium trophoblast migrate from the trophectoderm and invade into the stromal component of endometrium. Alterations on either process will lead to implantation failure or miscarriage. Volatile organic compounds (VOCs) such as benzene induce pregnancy complications, including preterm birth and miscarriages. The mechanism of this effect is unknown. The objective of this study was to elucidate the impact of benzene metabolite, Hydroquinone, on trophoblast function. We tested the hypothesis that Hydroquinone activates the Aryl hydrocarbon receptor (AhR) pathway modulating trophoblast migration and invasion.
First-trimester trophoblast cells (Sw.71) were treated with hydroquinone (6 and 25 μM). Trophoblast migration and invasion was evaluated using a 3D invasion/migration model. Gene expression was quantified by q-PCR and Western blot analysis.
Hydroquinone impairs trophoblast migration and invasion. This loss is associated with the activation of the AhR pathway which reduced the expression of Twist1and IFITM1. IFITM1 overexpression can rescue impaired trophoblast migration.
Our study highlights that hydroquinone treatment induces the activation of the AhR pathway in trophoblast cells, which impairs trophoblast invasion and migration. We postulate that activation of the AhR pathway in trophoblast suppress Twist1 and a subsequent IFITM1. Thus, the AhR-Twist1-IFITM1 axis represent a critical pathway involved in the regulation of trophoblast migration and it is sensitive to benzene exposure. These findings provide crucial insights into the molecular mechanisms underlying pregnancy complications induced by air pollution.
胚胎着床是一个严格调控的过程，对成功妊娠至关重要。囊胚附着在内膜上皮表面后，滋养层从滋养外胚层迁移并侵入子宫内膜的基质成分。这两个过程中的任何改变都会导致着床失败或流产。挥发性有机化合物（VOCs）如苯会导致妊娠并发症，包括早产和流产。其作用机制尚不清楚。本研究旨在阐明苯代谢物对羟苯（Hydroquinone）对滋养层功能的影响。我们提出假设，即 Hydroquinone 激活芳香烃受体（Aryl hydrocarbon receptor，AhR）通路，调节滋养层迁移和侵袭。
用 Hydroquinone（6 和 25 μM）处理早孕滋养层细胞（Sw.71）。使用 3D 侵袭/迁移模型评估滋养层迁移和侵袭。通过 q-PCR 和 Western blot 分析定量基因表达。
Hydroquinone 损害滋养层的迁移和侵袭。这种损失与 AhR 通路的激活有关，导致 Twist1 和 IFITM1 的表达减少。IFITM1 的过表达可以挽救受损的滋养层迁移。
我们的研究强调了 Hydroquinone 处理会在滋养层细胞中诱导 AhR 通路的激活，从而损害滋养层的侵袭和迁移。我们推测 AhR 通路在滋养层中的激活抑制了 Twist1，随后抑制 IFITM1。因此，AhR-Twist1-IFITM1 轴代表了参与调节滋养层迁移的关键途径，并且对苯暴露敏感。这些发现为空气污染引起的妊娠并发症的分子机制提供了重要的见解。
