Placentation Disruption by Perfluorooctanoic Acid and Perfluorooctanesulfonate in Human Trophoblast Organoids

IF 11.3 1区 环境科学与生态学 Q1 ENGINEERING, ENVIRONMENTAL
Mingzhu Li, , , Chenke Xu, , , Linwan Li, , , Fumei Gao, , , Cheng Xu, , , Yafei Yu, , , Chong Huang, , , Yanan Liu, , , Xinming Shen, , and , Jianying Hu*, 
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Abstract

Prenatal exposure to perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS) is associated with low birth weight, a condition often resulting from placental dysfunction. However, whether and how PFOA and PFOS affect human placentation and placental-specific functions remains unclear. In this study, we reconstructed a human trophoblast organoid model, incorporating a near-physiological proportion of extravillous trophoblast (EVT). The organoids were exposed to PFOA or PFOS for 7 days. Exposure to PFOA at 10 nM significantly increased the proportion of villous cytotrophoblast (CTB) cells, while reducing the proportion of EVT and syncytiotrophoblast (STB) cells at 10 and 100 nM, respectively. A similar pattern was observed with PFOS, albeit at concentrations 10 times higher than those of PFOA. Mechanistically, both PFOA and PFOS inhibited trophoblast differentiation by antagonizing the transcriptional activity of cAMP response element-binding protein (CREB). This disruption in placentation impaired placental function, as evidenced by significantly decreasing hormone secretion and invasion potential. Our investigation may provide mechanistic insight into the association of PFOA and PFOS with low birth weight observed in epidemiological studies, with PFOA demonstrating a stronger effect than PFOS. These findings may aid in evaluating the toxicity of emerging PFAS and support the development or selection of safer chemical alternatives.

Abstract Image

Abstract Image

人滋养细胞类器官中全氟辛酸和全氟辛烷磺酸对胎盘的破坏
产前接触全氟辛酸(PFOA)和全氟辛烷磺酸(PFOS)与低出生体重有关,低出生体重通常是由胎盘功能障碍引起的。然而,PFOA和PFOS是否以及如何影响人类胎盘和胎盘特异性功能仍不清楚。在这项研究中,我们重建了一个人类滋养细胞类器官模型,纳入了接近生理比例的体外滋养细胞(EVT)。类器官暴露于全氟辛烷磺酸或全氟辛烷磺酸7天。PFOA在10 nM下显著增加绒毛细胞滋养层细胞(CTB)的比例,而在10 nM和100 nM下分别降低EVT和合胞滋养层细胞(STB)的比例。在全氟辛烷磺酸中也观察到类似的情况,尽管其浓度比全氟辛烷磺酸高10倍。机制上,PFOA和PFOS均通过拮抗cAMP反应元件结合蛋白(CREB)的转录活性来抑制滋养细胞分化。胎盘的破坏损害了胎盘功能,这可以通过显著减少激素分泌和侵袭潜力来证明。我们的研究可能为流行病学研究中观察到的全氟辛烷磺酸和全氟辛烷磺酸与低出生体重之间的关系提供机制见解,其中全氟辛烷磺酸的影响比全氟辛烷磺酸更强。这些发现可能有助于评估新出现的PFAS的毒性,并支持开发或选择更安全的化学替代品。
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来源期刊
环境科学与技术
环境科学与技术 环境科学-工程:环境
CiteScore
17.50
自引率
9.60%
发文量
12359
审稿时长
2.8 months
期刊介绍: Environmental Science & Technology (ES&T) is a co-sponsored academic and technical magazine by the Hubei Provincial Environmental Protection Bureau and the Hubei Provincial Academy of Environmental Sciences. Environmental Science & Technology (ES&T) holds the status of Chinese core journals, scientific papers source journals of China, Chinese Science Citation Database source journals, and Chinese Academic Journal Comprehensive Evaluation Database source journals. This publication focuses on the academic field of environmental protection, featuring articles related to environmental protection and technical advancements.
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