Tossetta Giovanni, Fantone Sonia, Procopio Antonio Domenico, Pugnaloni Armanda, Gualtieri Alessandro Francesco, Marzioni Daniela
Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, Ancona, Italy.
Scientific Direction, IRCCS INRCA, Ancona, Italy.
Curr Res Toxicol. 2025 Mar 31;8:100231. doi: 10.1016/j.crtox.2025.100231. eCollection 2025.
It is known that mineral fibres can be found in placental tissues, but their effect is not known on these tissues. BeWo in vitro model of syncytiotrophoblast, the outer layer of maternal-foetal barrier, is necessary to understand if mineral fibres can alter placental cell turnover and consequently to influence the outcome of pregnancy. We performed in vitro experiments using chrysotile UICC (UICC), chrysotile Valmalenco (VM) and erionite (ERI) to investigate the potential cytotoxic effects of these mineral fibres on BeWo cells. We demonstrated that all fibres are toxic while only UICC fibres caused a DNA damage that the cells were not able to repair through RAD51 activity. In addition, we demonstrated that DNA replication is not altered while cyclin D1 showed a significant decrease in VM and UICC suggesting that the cell cycle is altered in G1 phase. Moreover, UICC increased active form of caspase 3 demonstrating that apoptosis can be induced in BeWo cells. We suggest that although morphological changes are not visible in BeWo cells treated with these mineral fibres, DNA damage can lead to altered placenta physiology that can be seen late when the damage at the foetal tissues has already occurred.
已知在胎盘组织中可发现矿物纤维,但它们对这些组织的影响尚不清楚。合体滋养层是母胎屏障的外层,建立BeWo体外模型对于了解矿物纤维是否会改变胎盘细胞更新从而影响妊娠结局至关重要。我们使用温石棉UICC(UICC)、瓦尔马伦科温石棉(VM)和毛沸石(ERI)进行了体外实验,以研究这些矿物纤维对BeWo细胞的潜在细胞毒性作用。我们证明所有纤维都具有毒性,而只有UICC纤维会导致DNA损伤,细胞无法通过RAD51活性进行修复。此外,我们证明DNA复制未改变,而细胞周期蛋白D1在VM和UICC中显著降低,这表明细胞周期在G1期发生改变。此外,UICC增加了半胱天冬酶3活性形式,表明可在BeWo细胞中诱导凋亡。我们认为,尽管在用这些矿物纤维处理的BeWo细胞中未观察到形态学变化,但DNA损伤可能导致胎盘生理改变,而这种改变在胎儿组织已经发生损伤时才会显现出来。