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Abstract Diseases like obesity and intestinal inflammation diseases are accompanied by dysbiosis of the gut microbiota (DSGM), which leads to various complications, including systemic metabolic disorders. DSGM reportedly impairs the fertility of male mice; however, the regulatory mechanism is unclear. Exosomes are molecular mediators of intercellular communication, but the regulation of spermatogenesis by non‐reproductive tissue‐originated exosomes remains unknown. The present study shows that DSGM altered the miRNA expression profile of mouse circulating exosomes and impaired spermatogenesis. Moreover, the single‐cell sequencing results indicate that circulating exosomes from mice with DSGM impaired spermatogenesis, while circulating exosomes from wild mice improved spermatogenesis by promoting meiosis. Further study demonstrates that DSGM leads to abnormal upregulation of miR‐211‐5p in gut‐derived circulating exosomes, which inhibited the expression of meiosis‐specific with coiled‐coil domain (Meioc) in the testes and impaired spermatogenesis by disturbing meiosis process. In summary, this study defines the important role of gut‐derived exosomes in connecting the “gut‐testis” axis.

In female mammals, the proliferation and apoptosis of granulosa cells (GCs) are critical in determining the fate of follicles and are influenced by various factors, including brain-derived neurotrophic factor (BDNF). Previous research has shown that BDNF primarily regulates GC proliferation through the PI3K/AKT, NF-kB, and CREB tumour pathways; however, the role of other molecular mechanisms in mediating BDNF-induced GC proliferation remains unclear. In this study, we investigated the involvement of the m6A reader YTH domain-containing family member 2 (YTHDF2) in BDNF-stimulated GC proliferation and its underlying mechanism. GCs were cultured in DMEM medium supplemented with varying BDNF concentrations (0, 10, 30, 75, and 150 ng/mL) for 24 h. The viability, number, and cell cycle of GCs were assessed using the CCK-8 assay, cell counting, and flow cytometry, respectively. Further exploration into YTHDF2’s role in BDNF-stimulated GC proliferation was conducted using RT-qPCR, Western blotting, and sequencing. Our findings indicate that YTHDF2 mediates the effect of BDNF on GC proliferation. Additionally, this study suggests for the first time that BDNF promotes YTHDF2 expression by increasing the phosphorylation level of the ERK1/2 signalling pathway. This study offers a new perspective and foundation for further elucidating the mechanism by which BDNF regulates GC proliferation.

Cadmium (Cd) is a major heavy metal toxicant found in industrial zones. Humans and animals are exposed to it through their diet, which results in various physiological problems. In the current study, the toxic effects of Cd on the liver were investigated by whole-transcriptome sequencing (RNA-seq) of the livers of Xiangxi heifers fed a diet with excess Cd. We randomly divided six healthy heifers into two groups. The first group received a control diet, whereas the second group received Cd-exceeding diets for 100 days. After 100 days, the livers were collected. A total of 551 differentially expressed mRNAs, 24 differentially expressed miRNAs, and 169 differentially expressed lncRNAs were identified (p < 0.05, |log2FC| >1). Differentially expressed genes (DEGs) were analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. We found that under Cd exposure, DEGs were enriched in the adenosine 5'-monophosphate–activated protein kinase pathway, which is involved in autophagy regulation, and the peroxisome proliferator–activated receptor pathway, which is involved in lipid metabolism. In addition, the apolipoprotein A4 gene, which has anti-inflammatory and antioxidant effects, the anti-apoptotic gene ATPase H+/K+ transporting the nongastric alpha2 subunit, and the cholesterol metabolism–associated gene endothelial lipase gene were significantly downregulated. C–X–C motif chemokine ligand 3, cholesterol 7α-hydroxylase, and stearoyl-CoA desaturase, which are involved in the development of fatty liver, were significantly upregulated. These genes revealed the main effects of Cd on the liver of Xiangxi yellow heifers. The current study provides insightful information regarding the DEGs involved in autophagy regulation, apoptosis, lipid metabolism, anti-inflammation, and antioxidant enzyme activity. These may serve as useful biomarkers for predicting and treating Cd-related diseases in the future.