Rsad2 mediates Bisphenol A-induced actin cytoskeletal disruption in mouse spermatocytes.

Bisphenol A (BPA) is widely exposed in populations worldwide and has negative effects on spermatogenesis both in animals and humans. The homeostasis of the actin cytoskeleton in the spermatogenic epithelium is crucial for spermatogenesis. Actin cytoskeleton destruction in the seminiferous epithelium is one of the important reasons for BPA-induced spermatogenesis disorder. However, the underlying molecular mechanisms remain largely unexplored. Herein, we explored the role and mechanism of Rsad2, an interferon-stimulated gene in BPA-induced actin cytoskeleton disorder in mouse GC-2 spermatocyte cell lines. After BPA exposure, the actin cytoskeleton was dramatically disrupted and the cell morphology was markedly altered accompanied by a significant increase in Rsad2 expression both in mRNA and protein levels in GC-2 cells. Furthermore, the phalloidin intensities and cell morphology were restored obviously when interfering with the expression of Rsad2 in BPA-treated GC-2 cells. In addition, we observed a significant decrease in intracellular ATP levels after BPA treatment, while the ATP level was obviously upregulated when knocking down the expression of Rsad2 in BPA-treated cells compared to cells treated with BPA alone. Moreover, Rsad2 relocated to mitochondria after BPA exposure in GC-2 cells. BPA promoted Rsad2 expression by activating type I IFN-signaling in GC-2 cells. In summary, Rsad2 mediated BPA-induced actin cytoskeletal disruption in GC-2 cells, which provided data to reveal the mechanism of BPA-induced male reproductive toxicity.

New methods based on a genetic algorithm back propagation (GABP) neural network and general regression neural network (GRNN) for predicting the occurrence of trihalomethanes in tap water.

Monitoring trihalomethanes (THMs) levels in water supply systems is of great significance in ensuring drinking water safety. However, THMs detection is a time-consuming task. Developing predictive THMs models using parameters that are easier to obtain is an alternative. To date, there is still no application of optimization algorithms and general regression neural networks in predicting disinfection by-products levels. This study was to explore the feasibility of back propagation neural network (BPNN), genetic algorithm back propagation (GABP) neural network and general regression neural network (GRNN) for predicting THMs occurrence in real water supply systems. The results showed that the BPNN models' prediction ability was limited (test rp = 0.571-0.857, N25 = 61.5 %-91.5 %). Optimized by the genetic algorithm (GA), GABP models were generated and exhibited better prediction performance (test rp = 0.573 and 0.696-0.863, N25 = 68.2 %-93.6 %). However, GABP models took a lot of time and their prediction performance was unstable. A GRNN was then used to generate simpler neural network models, and the resulting prediction performance was excellent (total trihalomethanes and bromodichloromethane: test rp = 0.657-0.824, N25 = 81.8 %-100 %). In general, GRNN was the best at predicting THMs concentrations among the three models. However, it is worth noting that the prediction accuracy of bromodichloromethane (BDCM) was not high, which may be due to the absence of key parameters affecting BDCM formation. Accurate predictions of THMs by GRNN with these nine water parameters made THMs monitoring in real water supply systems possible and practical.

Microplastics cause reproductive toxicity in male mice through inducing apoptosis of spermatogenic cells via p53 signaling.

BACKGROUND: Studies on male reproductive toxicity of microplastics are still scarce and the precise mechanism is not distinct. METHODS: C57BL/6 male mice were given oral gavage treatments treated with 5 µm (MPs) and 80 nm (NPs) polystyrene microplastics every day for 60 consecutive days in a row at dosages of 0, 10 and 40 mg/kg/d. The major damage of MPs and NPs were assessed by the assays in vivo and in vitro. Transcriptome sequencing was applied to screen the key involved pathways. RESULTS: In the 10 mg/kg/d NPs group, there was an increase in testicular organ coefficient, and in the 40 mg/kg/d MPs group, an increase in epididymal weight was observed. Vacuolization of spermatogenic cell layer, interstitial congestion, and germ cell apoptosis were found in the testes of MPs and NPs treatment mice at different dose groups. Higher apoptosis rate was observed in GC-2 cells after MPs and NPs treatment at different concentrations. Transcriptome analysis suggested that p53 pathway might be the key signal pathway of the cell apoptosis, and the expressions of p53 and other markers of cell apoptosis were indeed altered after exposure to MPs and NPs. CONCLUSIONS: MPs and NPs can cause reproductive toxicity in male mice through inducing apoptosis of spermatogenic cells via p53 signaling pathway, indicating MPs and NPs exposure be an unnegligible risk factor for reproductive health in male mice.