Gut-Derived Exosomes Mediate the Microbiota Dysbiosis-Induced Spermatogenesis Impairment by Targeting Meioc in Mice.

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.

Metabolomic Profiling of Female Mink Serum during Early to Mid-Pregnancy to Reveal Metabolite Changes.

Mink embryos enter a period of diapause after the embryo develops into the blastocyst, and its reactivation is mainly caused by an increase in polyamine. The specific process of embryo diapause regulation and reactivation remains largely unexamined. This study aimed to identify changes in metabolites in the early pregnancy of mink by comparing and analyzing in serum metabolites up to twenty-nine days after mating. Blood samples were taken on the first day of mating, once a week until the fifth week. Metabolomic profiles of the serum samples taken during this period were analyzed by ultra-performance liquid chromatography/mass spectrometry. Multivariate statistical analyses identified differential metabolite expression at different time points in both positive and negative ion modes. The levels of dopamine, tyramine, L-phenylalanine, L-tyrosine, tyrosine, L-kynurenine, L-lysine, L-arginine, D-ornithine, and leucine changed significantly. These metabolites may be associated with the process of embryo diapause and subsequent reactivation.

Comparison of lncRNA Expression in the Uterus between Periods of Embryo Implantation and Labor in Mice.

Uterine function during pregnancy is regulated mainly by progesterone (P4) and estrogen (E2). Serum P4 levels are known to fluctuate significantly over the course of pregnancy, especially during embryo implantation and labor. In this study, pregnant mice at E0.5, E4.5, E15.5, and E18.5 (n = 3/E) were used for an RNA-Seq-based analysis of mRNA and lncRNA expression. In this analysis, 1971 differentially expressed (DE) mRNAs, 493 known DE lncRNAs, and 1041 novel DE lncRNAs were found between E0.5 and E4.5 at the embryo implantation stage, while 1149 DE mRNAs, 192 known DE lncRNAs, and 218 novel DE lncRNAs were found between E15.5 and E18.5 at the labor stage. The expression level of lncRNA-MMP11 was significantly downregulated by P4 treatment on MSM cells, while lncRNA-ANKRD37 was significantly upregulated. Notably, 117 DE mRNAs, 19 known DE lncRNAs, and 31 novel DE lncRNAs were commonly expressed between the two stages, indicating that these mRNAs and lncRNAs may be directly or indirectly regulated by P4.

2-Methyl Nonyl Ketone From Houttuynia Cordata Thunb Alleviates LPS-Induced Inflammatory Response and Oxidative Stress in Bovine Mammary Epithelial Cells.

Mastitis is one of the most common diseases in dairy cows, causing huge economic losses to the dairy industry every year. Houttuynia Cordata Thunb ( H.cordata ) is a traditional Chinese herbal medicine that is widely used in clinical treatment. However, the therapeutic effect of 2-methyl nonyl ketone (MNK), the main volatile oil component in the aqueous vapor extract of H. cordata, on mastitis has been less studied. The purpose of this study was to investigate the protective effect and mechanism of MNK against lipopolysaccharide (LPS)-induced mastitis in vitro. The results showed that MNK pretreatment of the bovine mammary epithelial cell line (MAC-T) enhanced cell viability and inhibited LPS-induced reactive oxygen species (ROS) production and inflammatory response. MNK reduced the production of pro-inflammatory cytokines such as interleukin (IL) and tumor necrosis factor-α (TNF-α) by repressing LPS-induced activation of Toll-like receptor 4-nuclear factor-κB (TLR4-NF-κB) signaling pathway. In addition, MNK protected cells from inflammatory responses by blocking the downstream signaling of inflammatory factors. MNK also induced Heme Oxygenase-1 ( HO-1 ) production by Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway through AKT and extracellular signal-regulated kinase (ERK) pathways, thereby reducing LPS-induced oxidative damage for MAC-T cells. In conclusion, MNK played a protective role against LPS-induced cell injury. This provides a theoretical basis for the research and development of MNK as a novel therapeutic agent for mastitis.