Per- and polyfluoroalkyl substances (PFAS) have attracted significant attention due to their environmental toxicity. However, the detrimental impact of PFAS on the development of the female reproductive system remains controversial. In this study, we investigated the effects of three specific PFAS compounds perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) on ovarian development. Among these compounds, PFDA demonstrated the most pronounced cytotoxic effect on ovarian granulosa cells. The results showed that a 200 μM concentration of PFDA induced cell apoptosis via the intrinsic pathway by elevating reactive oxygen species (ROS) levels and activating Caspase-9 and Caspase-3. Furthermore, 200 μM PFDA triggered necroptosis, a form of regulated cell death (RCD), through the receptor-interacting serine/threonine kinase 1 (RIPK1), receptor interacting protein kinase 3 (RIPK3), and mixed-lineage kinase domain-like protein (MLKL) axis, mediated by inhibition of the canonical apoptosis proteolytic enzyme Caspase-8. In vivo experiments confirmed that mice exposed to PFDA displayed a significantly reduced ovarian index compared to the control group, accompanied by evident follicular atresia. Ovarian tissues from the PFDA-exposed group showed upregulated necroptosis markers, which were effectively mitigated by inhibiting the phosphorylation of RIPK1 at Ser166. Importantly, this study provides the first evidence that PFDA disrupts ovarian development through a novel mechanism involving the RIPK1-mediated necroptosis pathway, alongside the detection of the intrinsic apoptosis pathway. This greatly expands our insight into the effects of PFDA on cell death. This finding highlights the potential public health hazards associated with PFDA exposure and emphasizes the need for further research to fully understand its broader implications.
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http://dx.doi.org/10.1016/j.ecoenv.2024.117268 | DOI Listing |
Mar Pollut Bull
December 2024
Institute of Marine Research (IMR), P.O. 1870 Nordnes, NO-5817 Bergen, Norway. Electronic address:
Poly- and perfluoroalkyl substances (PFAS) are of global concern due to their persistence and harmful effects on human health and ecosystems. However, research on PFAS in the River Nile and across Africa is limited. This study provides the first assessment of PFAS contamination in fish livers from the River Nile in Sudan, using ultra-high-performance liquid chromatography and high-resolution mass spectrometry.
View Article and Find Full Text PDFEnviron Res
December 2024
Institut de recherche en santé, environnement et travail (Irset), Univ Rennes, Inserm, EHESP, 9 Av. Professeur Léon Bernard, Rennes, France. Electronic address:
Introduction: While a number of studies have examined the effects of prenatal exposure to per- and polyfluoroalkyl substances (PFAS) on childhood obesity, the results reported have been inconsistent and few studies have integrated biological markers. The aim of this study was to investigate the associations between prenatal exposure to PFAS and cardiometabolic health parameters at age 12, taking pubertal stage into consideration.
Method: This study included 394 mother-child pairs enrolled in the PELAGIE mother-child cohort (France).
Environ Res
December 2024
Department of Occupational and Environmental Health, Ministry of Education Key Laboratory of Environment and Health, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address:
Background: The association between per- and polyfluoroalkyl substances (PFAS) and mitochondrial DNA copy number (mtDNAcn) in children, and the potential impact of estimated glomerular filtration rate (eGFR) on this association, remains unclear.
Methods: We conducted a panel study with up to 3 surveys over 3 seasons in Weinan and Guangzhou, China. A total of 284 children aged 4-12 years were available, with 742 measurements of 11 PFAS and mtDNAcn.
Ecotoxicol Environ Saf
December 2024
Department of Health Inspection and Quarantine, School of Public Health, Fujian Medical University, Fuzhou, Fujian 350122, China. Electronic address:
Perfluorodecanoic acid (PFDA) is a typical perfluoroalkyl substances frequently encountered in populations, posing significant risks to human health. However, research on the effects of PFDA exposure on organism metabolism and related pathogenic mechanisms is severely lacking. In this study, serum and liver samples of C57BL/6 J mice exposed to different doses of PFDA were analyzed by UPLC-HRMS-based metabolomics and lipidomics techniques.
View Article and Find Full Text PDFCrit Rev Toxicol
December 2024
Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used widely in industrial and commercial applications. Concerns exist about their potential link to cancer risk as possible endocrine-disrupting chemicals. We conducted a meta-analysis to evaluate the dose-response relationship between PFAS, perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorohexanesulfonic acid (PFHxS) exposure and risk of breast, prostate, colorectal, and ovarian cancers.
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