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Both epidemiological investigation and animal experiments demonstrated that pre-/postnatal exposure to perfluorooctane sulfonic acid (PFOS) could induce neurodevelopmental disorders. Previous studies showed that astrocyte was involved in PFOS-induced neurotoxicity, while little information is available. In the present study, the role of astrocyte-derived calmodulin-dependent protein kinase II (CaMKII)-phosphorylated discs large homolog 1 (DLG1) signaling in PFOS eliciting cytotoxicity in neuron was explored with primary cultured hippocampal astrocyte and neuron. The application of PFOS showed a decreased cell viability, synapse length and glutamate transporter 1 (GLT-1) expression, but an increased CaMKII, DLG1 and cyclic AMP response element binding protein (CREB) expression in primary cultured astrocyte. With 2-(2-hydroxyethylamino)-6-aminohexylcarbamic acid tert-butyl ester-9-isopropylpurine (CK59), the CaMKII inhibitor, the disturbed cell viability and molecules induced by PFOS could be alleviated (CREB expression was excluded) in astrocytes. The cytotoxic effect of neuron exposed to astrocyte conditional medium collected from PFOS (PFOS-ACM) pretreated with CK59 was also decreased. These results indicated that PFOS mediated GLT-1 expression through astrocyte-derived CaMKII-DLG signaling, which might be associated with injuries on neurons. The present study gave an insight in further exploration of mechanism in PFOS-induced neurotoxicity. [ABSTRACT FROM AUTHOR]

Aims: Testis and sperm are particularly susceptible to inflammation and oxidative stress. Although hydrogen sulfide (H2S) has been considered an important biological signaling molecule in inflammatory and oxidative stress processes, its role in the male reproductive system was poorly understood. The aim of this study was to investigate the role of H2S in the regulation of male reproductive system. Results: We found that both subfertile and infertile patients, especially asthenospermic patients, exhibited decreased concentration of H2S in their seminal plasma and diminished expression of H2S-generating enzyme (cystathionine β-synthase [CBS]) in sperm. Supplying exogenous H2S to semen improved sperm motility of these asthenospermic patients. Furthermore, decreased sperm motility was observed in animal models with a defective in H2S generation such as lipopolysaccharide-treated mice, diabetic mice, and CBS-deficient mice. Our research showed that stress-induced reductions of endogenous H2S production and CBS expression are correlated with impaired spermatogenesis and a defective blood–testis barrier. Supplying exogenous H2S or overexpressing CBS could relieve the spermatogenic failure. This occurred primarily through the combination of anti-inflammatory and antioxidative effects. Innovation: These results provide the first indication that H2S is important for maintaining male fertility and protecting testicular function. Conclusion: H2S plays an important role in spermatogenic failure and testicular dysfunction mainly by its anti-inflammatory and antioxidative effects. Antioxid. Redox Signal. 28, 1447–1462. [ABSTRACT FROM AUTHOR]

Perfluorooctane sulfonate (PFOS) is a potential neurotoxicant reported by epidemiological investigations and experimental studies, while the underlying mechanisms are still unclear. Astrocytes not only support for the construction of neurons, but also conduct neuronal functions through glutamate-glutamine cycle in astrocyte-neuron crosstalk. In the present study, the effect of PFOS exposure on rat primary hippocampal neurons or cortex astrocytes was evaluated. Then the role of the astrocytes in PFOS-induced toxic effect on neurons was explored with astrocyte-neuron co-culture system. Exposure of rat primary hippocampal neurons to PFOS has led to oxidation-antioxidation imbalance, increased apoptosis and abnormal autophagy. The adverse effect of PFOS on rat primary cortex astrocytes manifested in the form of altered extracellular glutamate and glutamine concentrations, decreased glutamine synthase activity, as well as decreased gene expression of glutamine synthase, glutamate transporters and glutamine transporters in the glutamate-glutamine cycle. Especially, the alleviation of PFOS-inhibited neurite outgrowth in neurons could be observed in astrocyte-neuron co-culture system, though the ability of astrocytes in fostering neurite outgrowth was affected by PFOS. These results indicated that both astrocytes and neurons might be the targets of PFOS-induced neurotoxicity, and astrocytes could protect against PFOS-inhibited neurite outgrowth in primary cultured neurons. Our research might render some information in explaining the mechanisms of PFOS-induced neurotoxicity. [ABSTRACT FROM AUTHOR]