Cyfluthrin, a typical type II pyrethroid pesticide, is widely used in house hygiene and agricultural pest control. Several epidemiological investigations have found that maternal pyrethroid exposure is connected to adverse pregnancy outcomes. However, the underlying mechanisms remain to be elucidated. Thus, we evaluated the effect of cyfluthrin exposure during pregnancy on placenta development in vivo. In the current study, Pregnant SD rats were randomly divided into four groups and administered 6.25, 12.5, and 25 mg/kg body weight cyfluthrin or an equivalent volume of corn oil by gavage from GD0 to GD19. The results have shown that gestational exposure to cyfluthrin exerted no effect on the fetal birth defect, survival to PND4, or fetal resorption and death. However, live fetuses and implantation sites significantly decreased in the high-dose cyfluthrin-treated group. Moreover, a significant reduction in placenta weight and diameter was observed in rats. Correspondingly, the fetal weight and crown-rump length from dams exposed to cyfluthrin were reduced. Cyfluthrin-treat groups, the total area of the placenta, spongiotrophoblast area, and labyrinth area had abnormal changes. Meanwhile, the area of blood sinusoid and CD34-positive blood vessel numbers in the placenta were considerably reduced, as well as abnormal expression of placental pro-angiogenic and anti-angiogenic factors in dams exposed to cyfluthrin. Further observation by transmission electron microscopy revealed significant changes in the ultrastructure of the medium-dose and high-dose groups. Additional experiments showed gestational exposure to cyfluthrin inhibited proliferation and induced apoptosis of placentas, as decreased PCNA-positive cells and increased TUNEL-positive cells. Furthermore, western blot and qPCR analysis revealed that gestational exposure to medium-dose and high-dose cyfluthrin increased the expression of GRP78, and three downstream mRNA and proteins (p-eIF2α, ATF4, and CHOP) of the PERK signaling, indicating that endoplasmic reticulum (ER) stress-mediated PERK/eIF2α/ATF4/CHOP signaling pathway in rat placentas was activated. Our study demonstrated that gestational exposure to cyfluthrin leads to placental developmental disorder, which might be associated with ER stress-mediated PERK signaling pathway.

Cyfluthrin is a widely used insecticide, and studies have shown that its exposure during pregnancy is associated with neurobehavioral abnormalities in offspring, but the mechanism of toxicity is unknown. In this study, we observed the neurodevelopmental toxicity of Cyfluthrin in rat offspring of different ages due to pregnancy exposure, which manifested a series of impairments such as persistent cognitive impairment, neuronal loss in hippocampal tissues, synaptic damage, and altered expression of neurodevelopmental-related factors. Hippocampal scRNA-seq in neonatal rats showed specific cellular responses to prenatal Cyfluthrin exposure. Through DEG intergroup difference analysis, intercellular communication analysis, and mimetic timing analysis, we found that the change in the fate of neural stem cells - alterations in differentiation direction, proliferation, and apoptosis levels - was the main cause of the offspring's developmental toxicity induced by prenatal Cyfluthrin exposure. This inference was verified by our in - vivo and ex - vivo experiments. Our study first constructed a single - cell atlas of the offspring's brain hippocampus exposed to Cyfluthrin during pregnancy. It warns about pesticide intake during pregnancy and nursing in women and provides a theoretical basis for neurodevelopmental toxicity from early - life exposure to environmental pollutants.

Hexafluoropropylene oxide trimer acid (HFPO-TA), a widely used replacement for perfluorooctanoic acid (PFOA), has recently been detected in various environmental media and human biological samples. Its high environmental persistence and potential for bioaccumulation have raised growing concerns about its health risks. However, the molecular mechanisms underlying its male reproductive toxicity remain poorly understood. This study systematically evaluated the effects of HFPO-TA on testosterone synthesis using in vivo mouse exposure models and in vitro Leydig cell models. HFPO-TA exposure caused significant testicular damage and reduced sperm quality in mice. Additional studies revealed that HFPO-TA notably inhibited testosterone biosynthesis, both in vivo and in vitro. Mechanistic studies identified ferroptosis as the key mechanism mediating HFPO-TA-induced testosterone synthesis impairment. Furthermore, HFPO-TA exposure downregulated the expression of the demethylase FTO, leading to an abnormal elevation of m⁶A modification levels. During this process, the m⁶A reader protein IGF2BP2 enhanced its binding to Ncoa4 mRNA, thereby promoting its stability and driving ferroptosis. Additional validation in immortalized human Leydig cells and in vivo pharmacological intervention experiments provided further support for these findings. Overall, this study identifies the FTO-m⁶A-IGF2BP2-NCOA4 axis as a key epitranscriptomic pathway involved in HFPO-TA-induced Leydig cell dysfunction. These findings provide crucial scientific evidence for the risk assessment of emerging per- and polyfluoroalkyl substances and identify potential molecular targets for intervention against pollutant-induced male reproductive impairment.

This study employed an integrated network toxicology and molecular docking approach to explore the molecular mechanisms by which the herbicide 2,4-Dichlorophenoxyacetic acid (2,4-D) may contribute to neurodegenerative diseases (NDDs). We identified 89 common targets through the intersection of potential 2,4-D-related targets and NDD-associated genes. Among these, 12 core targets—including NFKB1, PPARG, SERPINE1, NOS3, and NFE2L2—were highlighted via protein–protein interaction network analysis. Functional enrichment revealed that these targets are involved in key pathways such as inflammatory response, oxidative stress, metabolic dysregulation, and synaptic dysfunction. Molecular docking further confirmed strong binding affinities between 2,4-D and all core targets (binding energy ≤ −5.1 kcal·mol⁻¹). These findings systematically reveal, for the first time, a multi-target and multi-pathway mechanism through which 2,4-D may induce neuronal injury, providing a theoretical basis for assessing environmental risk in neurodegeneration.

(1) Background: Acetamiprid, a widely used neonicotinoid insecticide, has increasingly drawn people’s attention to its potential reproductive toxicity risks. Although existing studies have shown that exposure to acetamiprid can cause testicular damage, its underlying molecular mechanism has not been fully elucidated. (2) Methods: This study established a mouse model of acetamiprid exposure via free drinking water and combined it with in vitro culture of TM3 cells, aiming to explore the toxic effects of acetamiprid on testicular tissue and its potential mechanism. (3) Results: Acetamiprid exposure induced significant pathological damage to the testicular tissue of mice and significantly reduced sperm quality. Further mechanism studies have shown that acetamiprid down-regulates the expression of RNA demethylase ALKBH5, leading to an overall increase in m⁶A modification levels, thereby inhibiting the activity of the PI3K/AKT signaling pathway and ultimately inducing apoptosis of TM3 cells. (4) Conclusions: In conclusion, this study, by integrating both internal and external models, has revealed a molecular mechanism by which acetamiprid is involved in testicular injury through epigenetic pathways, providing scientific basis and mechanism clues for assessing reproductive hazards caused by exposure to environmental toxins.