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Infertility is a global health problem affecting millions of people of reproductive age worldwide, with approximately half caused by males. Chitosan oligosaccharide (COS) has strong antioxidant capacity, but its impact on the male reproductive system has not been effectively evaluated. To address this, we integrated RNA-seq, serum metabolomics and intestinal 16â¯S rDNA analysis to conduct a comprehensive investigation on the male reproductive system. The results showed that COS has potential targets for the treatment of oligospermia, which can promote the expression of meiotic proteins DDX4, DAZL and SYCP1, benefit germ cell proliferation and testicular development, enhance antioxidant capacity, and increase the expression of testicular steroid proteins STAR and CYP11A1. At the same time, COS can activate PI3K-Akt signaling pathway in testis and TM3 cells. Microbiome and metabolomics analysis suggested that COS alters gut microbial community composition and cooperates with serum metabolites to regulate spermatogenesis. Therefore, COS promotes male reproduction by regulating intestinal microorganisms and serum metabolism, activating PI3K-Akt signaling pathway, improving testicular antioxidant capacity and steroid regulation.
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Selenium (Se), a component of selenoproteins and selenocompounds in the human body, is crucial for the development of male reproductive organs, DNA synthesis, thyroid hormone, metabolism, and defence against infections and oxidative damage. In the testis, it must exceed a desirable level since either a shortage or an overabundance causes aberrant growth. The antioxidant properties of selenium are essential for preserving human reproductive health. Selenoproteins, which have important structural and enzymatic properties, control the biological activities of Se primarily. These proteins specifically have a role in metabolism and a variety of cellular processes, such as the control of selenium transport, thyroid hormone metabolism, immunity, and redox balance. Selenium nanoparticles (SeNPs) are less hazardous than selenium-based inorganic and organic materials. Upon being functionalized with active targeting ligands, they are both biocompatible and capable of efficiently delivering combinations of payloads to particular cells. In this review, we discuss briefly the chemistry, structure and functions of selenium and milestones of selenium and selenoproteins. Next we discuss the various factors influences male infertility, biological functions of selenium and selenoproteins, and role of selenium and selenoproteins in spermatogenesis and male fertility. Furthermore, we discuss the molecular mechanism of selenium transport and protective effects of selenium on oxidative stress, apoptosis and inflammation. We also highlight critical contribution of selenium nanoparticles on male fertility and spermatogenesis. Finally ends with conclusion and future perspectives.
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Global aflatoxin B1 (AFB1) contamination is inevitable, and it can significantly damage testicular development. However, the current mechanism is confusing. Here, by integrating the transcriptome, microbiome, and serum metabolome, we comprehensively explain the impact of AFB1 on testis from the gut-metabolism-testis axis. Transcriptome analysis suggested that AFB1 exposure directly causes abnormalities in testicular inflammation-related signalling, such as tumor necrosis factor (TNF) pathway, and proliferation-related signalling pathways, such as phosphatidylinositide 3-kinases-protein kinase B (PI3K-AKT) pathway, which was verified by immunofluorescence. On the other hand, we found that upregulated inflammatory factors in the intestine after AFB1 exposure were associated with intestinal microbial dysbiosis, especially the enrichment of Bacilli, and enrichment analysis showed that this may be related to NLR family pyrin domain containing 3 (NLRP3)-mediated NOD-like receptor signalling. Also, AFB1 exposure caused blood metabolic disturbances, manifested as decreased hormone levels and increased oxidative stress. Significantly, B. licheniformis has remarkable AFB1 degradation efficiency (> 90%). B. licheniformis treatment is effective in attenuating gut-testis axis damage caused by AFB1 exposure through the above-mentioned signalling pathways. In conclusion, our findings indicate that AFB1 exposure disrupts testicular development through the gut-metabolism-testis axis, and B. licheniformis can effectively degrade AFB1.
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Bacillus licheniformis , Testículo , Masculino , Humanos , Aflatoxina B1/toxicidad , Aflatoxina B1/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , MetabolomaRESUMEN
BACKGROUND: Aflatoxin B1 (AFB1), one of the most prevalent contaminants in human and animal food, impairs the immune system, but information on the mechanisms of AFB1-mediated macrophage toxicity is still lacking. METHODS AND RESULTS: In this study, for the first time, we employed whole transcriptome sequencing technology to explore the molecular mechanism by which AFB1 affects the growth of porcine alveolar macrophages (PAM). We found that AFB1 exposure reduced the proliferative capacity of PAM and prevented cell cycle progression. Based on whole transcriptome analysis, RT-qPCR, ICC and RNAi, we verified the role and regulatory mechanism of the competing endogenous RNA (ceRNA) network in the process of AFB1 exposure affecting the growth of PAM. CONCLUSIONS: We found that AFB1 induced MSTRG.43,583, MSTRG.67,490, MSTRG.84,995, and MSTRG.89,935 to competitively bind miR-219a, miR-30b-3p, and miR-30c-1-3p, eliminating the inhibition of its target genes CACNA1S, RYR3, and PRKCG. This activated the calcium signaling pathway to regulate the growth of PAM. These results provide valuable information on the mechanism of AFB1 exposure induced impairment of macrophage function in humans and animals.
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Aflatoxina B1 , MicroARNs , Humanos , Animales , Porcinos , Aflatoxina B1/toxicidad , Aflatoxina B1/metabolismo , Macrófagos Alveolares/metabolismo , Señalización del Calcio , Macrófagos/metabolismo , MicroARNs/genética , MicroARNs/metabolismoRESUMEN
All forms of life produce nanosized extracellular vesicles called exosomes, which are enclosed in lipid bilayer membranes. Exosomes engage in cell-to-cell communication and participate in a variety of physiological and pathological processes. Exosomes function via their bioactive components, which are delivered to target cells in the form of proteins, nucleic acids, and lipids. Exosomes function as drug delivery vehicles due to their unique properties of innate stability, low immunogenicity, biocompatibility, biodistribution, accumulation in desired tissues, low toxicity in normal tissues, and the stimulation of anti-cancer immune responses, and penetration capacity into distance organs. Exosomes mediate cellular communications by delivering various bioactive molecules including oncogenes, oncomiRs, proteins, specific DNA, messenger RNA (mRNA), microRNA (miRNA), small interfering RNA (siRNA), and circular RNA (circRNA). These bioactive substances can be transferred to change the transcriptome of target cells and influence tumor-related signaling pathways. After considering all of the available literature, in this review we discuss the biogenesis, composition, production, and purification of exosomes. We briefly review exosome isolation and purification techniques. We explore great-length exosomes as a mechanism for delivering a variety of substances, including proteins, nucleic acids, small chemicals, and chemotherapeutic drugs. We also talk about the benefits and drawbacks of exosomes. This review concludes with a discussion future perspective and challenges. We hope that this review will provide us a better understanding of the current state of nanomedicine and exosome applications in biomedicine.
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Exosomas , MicroARNs , Neoplasias , Ácidos Nucleicos , Exosomas/metabolismo , Distribución Tisular , Sistemas de Liberación de Medicamentos/métodos , MicroARNs/metabolismo , Proteínas/metabolismo , ARN Interferente Pequeño/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismoRESUMEN
Aflatoxins B1 (AFB1), a type I carcinogen widely present in the environment, not only poses a danger to animal husbandry, but also poses a potential threat to human reproductive health, but its mechanism is still unclear. To address this question, multi-omics were performed on porcine Sertoli cells and mice testis. The data suggest that AFB1 induced testicular damage manifested as decreased expression of GJA1, ZO1 and OCCLUDIN in mice (p < 0.01) and inhibition of porcine Sertoli cell proliferation. Transcriptomic analysis suggested changes in noncoding RNA expression profiles that affect the cell cycle-related Ras/PI3K/Akt signaling pathway after AFB1 exposure both in mice and pigs. Specifically, AFB1 caused abnormal cell cycle of testis with the characterization of decreased expressions of CCNA1, CCNB1 and CDK1 (p < 0.01). Flow cytometry revealed that the G2/M phase was significantly increased after AFB1 exposure. Meanwhile, AFB1 downregulated the expressions of Ras, PI3K and AKT both in porcine Sertoli cell (p < 0.01) and mice testis (p < 0.01). Metabolome analysis verified the alterations in the PI3K/Akt signaling pathway (p < 0.05). Moreover, the joint analysis of metabolome and microbiome found that the changes of metabolites were correlated with the expression of flora. In conclusion, we have demonstrated that AFB1 impairs testicular development via the cell cycle-related Ras/PI3K/Akt signaling.
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Aflatoxina B1 , Ciclo Celular , Proteínas Proto-Oncogénicas c-akt , Animales , Humanos , Masculino , Ratones , Aflatoxina B1/toxicidad , División Celular , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , PorcinosRESUMEN
Naringin (NAR) is a dihydroflavonoid with various biological activities and pharmacological effects, especially natural antioxidant activity. To gain a better understanding of the effects of NAR on the reproductive system, especially spermatogenesis, we employed western blotting, immunofluorescence, immunohistochemistry, metabolomics and microbiomics to comprehensively dissect the impact of NAR on spermatogenesis. NAR promotes germ cell proliferation and testicular development, and promotes the secretion of sex hormones. Microbiomic and metabonomic analysis showed that NAR improved intestinal microflora and cooperated with serum metabolites to regulate spermatogenesis. Therefore, NAR is beneficial for male reproduction by regulating intestinal microorganisms and serum metabolism.
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Flavanonas , Masculino , Humanos , Flavanonas/farmacología , Espermatogénesis , AntioxidantesRESUMEN
Considering that research has mainly focussed on how excessive iron supplementation leads to reproductive cytotoxicity, there is a lack of in-depth research on reproductive system disorders caused by iron deficiency. To gain a better understanding of the effects of iron deficiency on the reproductive system, especially spermatogenesis, we first constructed a mouse model of iron deficiency. We employed multi-omic analysis, including transcriptomics, metabolomics, and microbiomics, to comprehensively dissect the impact of iron deficiency on spermatogenesis. Moreover, we verified our findings in detail using western blot, immunofluorescence, immunohistochemistry, qRT-PCR and other techniques. Microbiomic analysis revealed altered gut microbiota in iron-deficient mice, and functional predictive analysis showed that gut microbiota can regulate spermatogenesis. The transcriptomic data indicated that iron deficiency directly alters expression of meiosis-related genes. Transcriptome data also revealed that iron deficiency indirectly regulates spermatogenesis by affecting hormone synthesis, findings confirmed by metabolomic data, western blot and immunofluorescence. Interestingly, competing endogenous RNA networks also play a vital role in regulating spermatogenesis after iron deficiency. Taken together, the data elucidate that iron deficiency impairs spermatogenesis and increases the risk of male infertility by affecting hormone synthesis and promoting gut microbiota imbalance.
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Deficiencias de Hierro , Masculino , Ratones , Animales , Espermatogénesis , Metabolómica , Hierro , HormonasRESUMEN
In this study, the synthesis parameters of the lotus root polysaccharide iron complex (LRPF) were determined and optimized by response surface methodology. Under the optimum preparation conditions, the pH of the solution was 9, the ratio of M (trisodium citrate): m (lotus root polysaccharide) was 0.45, the reaction time was 3 h. UV spectroscopy, thermogravimetry, FT-IR spectroscopy, X-ray diffraction, CD, and NMR were used for the characterization of the LRPF. LRPF has good stability and easily releases iron ions under artificial gastrointestinal conditions. LRPF exhibited antioxidant activity in vitro and can significantly improve the antioxidant activity in vivo. In addition, LRPF has a good effect in the treatment of iron deficiency anemia in model mice, impacts the gut microbiome, and reduces the iron deficiency-induced perniciousness by regulating steroid hormone biosynthesis. Therefore, LRPF can be used as a nutritional supplement to treat and prevent iron-deficiency anemia and improve human immunity.
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Anemia Ferropénica , Antioxidantes , Ratones , Humanos , Animales , Antioxidantes/farmacología , Antioxidantes/química , Espectroscopía Infrarroja por Transformada de Fourier , Anemia Ferropénica/tratamiento farmacológico , Hierro/química , Polisacáridos/farmacología , Polisacáridos/química , Esteroides , HormonasRESUMEN
Di(2-ethylhexyl)phthalate (DEHP) has proven characteristics of an endocrine-disrupting compound (EDC), which can threaten the reproductive health of humans and other animals. In mammals, a series of chromosomal events occur during the meiotic stage of oocytes. External toxins may enter the body and cause infertility and other related diseases. Therefore, it is crucial to explore the influence of DEHP exposure on the molecular mechanism of germ cell meiosis. We used single-cell RNA sequencing (scRNA-seq) to analyse the ovaries of foetal mice at embryonic day 12.5 (E12.5) and E14.5 after maternal DEHP exposure. DEHP exposure further activated the pathways related to DNA repair in germ cells, increased the expression of genes related to DNA damage and changed the developmental trajectory of germ cells. DEHP exposure may affect the proliferation of pregranulosa (PG) cells. Moreover, DEHP exposure altered the signal transduction between PG cells and germ cells. We showed that DEHP affects meiosis by causing DNA damage in oocytes and disrupting the signal transduction between PG cells and germ cells. These results provide a strong theoretical basis for the prevention and treatment of DEHP-mediated female reproductive health problems.
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Dietilhexil Ftalato , Animales , Dietilhexil Ftalato/metabolismo , Dietilhexil Ftalato/toxicidad , Femenino , Células Germinativas , Humanos , Mamíferos , Meiosis , Ratones , Oocitos/metabolismo , TranscriptomaRESUMEN
With the increasing global incidence of infertility, the influence of environmental factors, lifestyle habits, and nutrients on reproductive health has gradually attracted the attention of researchers. The quantity and quality of sperm play vital roles in male fertility, and both characteristics can be affected by external and internal factors. In this review, the potential role of genetic, environmental, and endocrine factors; nutrients and trace elements in male reproductive health, spermatozoa function, and fertility potency and the underlying mechanisms are considered to provide a theoretical basis for clinical treatment of infertility.