Study summary · research use only
Oligoasthenozoospermia is alleviated in a mouse model by [Gly14]-humanin-mediated attenuation of oxidative stress and ferroptosis
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This mouse study investigated whether [Gly14]-Humanin (HNG) affects oligoasthenozoospermia induced by cyclophosphamide (CP), and the underlying mechanism. Mice treated with CP to model oligoasthenozoospermia received saline or HNG, after which testis weight, organ indices, testicular structure, sperm counts and motility, litter size, and serum testosterone were measured, along with RNA sequencing of testicular tissue. In TM3, TM4, GC1, and GC2 cells exposed to erastin to induce ferroptosis, cells were treated with HNG or HNG plus ML385. HNG treatment was associated with improved testis and sperm parameters and increased litter size and testosterone in model mice, along with changes in ferroptosis-related proteins, decreased ROS, MDA, and Fe2+, and increased GSH via the Nrf2/GPX4 pathway; these effects were blocked by ML385.
Abstract
Oligoasthenozoospermia is a common cause of male infertility, for which effective treatments are urgently needed. Humanin (HN) is a peptide associated with this condition. To investigate the ameliorative effect of [Gly14]-Humanin (HNG) on oligoasthenozoospermia and the mechanisms. Mice were treated with cyclophosphamide (CP) to construct a mice model of oligoasthenozoospermia. The resulting model mice were treated with saline or HNG. Subsequently, the testis weights, organ indices, testicular structure, sperm counts and motilities, litter sizes, and serum testosterone concentrations of the mice were determined. Differential gene expression in testicular tissues was determined by RNA sequencing. TM3, TM4, GC1, and GC2 cells were exposed to erastin to induce ferroptosis, followed by treatment with HNG or HNG + ML385 (a nuclear factor erythroid 2-related factor 2 inhibitor). Levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and ferrous ions (Fe2+) were determined and their expression of ferroptosis-related proteins was determined by immunofluorescence and western blot. The HNG treatment improved testis and sperm parameters and increased litter size and serum testosterone concentrations in model mice. Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analysis revealed significant differential expression of ferroptosis-related genes. The expression of ferroptosis-related proteins increased in testicular tissues after the HNG treatment. The concentrations of ROS, MDA, and Fe2+ decreased and the concentrations of GSH increased in testicular tissues and in TM3 and TM4 cells after HNG treatment. In vitro experiments confirmed that HNG activated the nuclear factor erythroid 2-related factor 2/glutathione peroxidase 4 (Nrf2/GPX4) pathway. However, these effects of HNG were blocked by ML385 treatment. HNG demonstrated a therapeutic effect on oligoasthenozoospermia in a mouse model by reducing oxidative stress and ferroptosis. In TM3 and TM4 cells, HNG attenuated cellular oxidative stress and inhibited ferroptosis via the Nrf2/GPX4 pathway.
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