RESUMO
Telocytes (TCs) are a type of stromal cell discovered in the various organs of different animals and have many potential functions, including angiogenesis, signalling, and substance transport. However, the TCs have not been detected in the testis or epididymis of Tibetan sheep. This study investigated the position, characteristics, and distribution of TCs in the testis and epididymis of Tibetan sheep using transmission electron microscopy (TEM), toluidine blue staining, immunohistochemistry, and double immunofluorescence to elucidate their possible functions. TEM revealed that TCs were often found near basement membranes and capillaries and were characterised by large nuclei, elongated cytoplasmic protrusions, and many secretory vesicles. We also observed via toluidine staining that TCs were present near basement membrane and interstitial capillaries. Immunohistochemistry and double immunofluorescence revealed the positive expression of CD117, vimentin, platelet derived growth factor receptor α(PDGFRα), PDGFRα + CD117, and PDGFRα + vimentin in TCs. Additionally, we inferred that TCs participates in the formation of the blood-testis and blood-epididymis barriers, as well as in material transport and a stable microenvironment. This study presents the first evidence of the presence of TCs near the basement membrane and blood vessels in the testis and epididymis of Tibetan sheep. These findings provide new insights into the function of TCs in the reproductive systems of plateau animals.
Assuntos
Epididimo , Telócitos , Testículo , Animais , Masculino , Telócitos/metabolismo , Telócitos/citologia , Telócitos/ultraestrutura , Epididimo/metabolismo , Epididimo/citologia , Ovinos , Testículo/metabolismo , Testículo/citologia , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Microscopia Eletrônica de Transmissão , Tibet , Vimentina/metabolismo , Imuno-Histoquímica , Membrana Basal/metabolismo , Membrana Basal/ultraestruturaRESUMO
ARL13B is a small regulatory GTPase that controls ciliary membrane composition in both motile cilia and non-motile primary cilia. In this study, we investigated the role of ARL13B in the efferent ductules, tubules of the male reproductive tract essential to male fertility in which primary and motile cilia co-exist. We used a genetically engineered mouse model to delete Arl13b in efferent ductule epithelial cells, resulting in compromised primary and motile cilia architecture and functions. This deletion led to disturbances in reabsorptive/secretory processes and triggered an inflammatory response. The observed male reproductive phenotype showed significant variability linked to partial infertility, highlighting the importance of ARL13B in maintaining a proper physiological balance in these small ducts. These results emphasize the dual role of both motile and primary cilia functions in regulating efferent duct homeostasis, offering deeper insights into how cilia related diseases affect the male reproductive system.
Assuntos
Fatores de Ribosilação do ADP , Cílios , Masculino , Animais , Cílios/metabolismo , Cílios/fisiologia , Fatores de Ribosilação do ADP/metabolismo , Fatores de Ribosilação do ADP/genética , Camundongos , Infertilidade Masculina/genética , Infertilidade Masculina/fisiopatologia , Infertilidade Masculina/patologia , Camundongos Knockout , Epididimo/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Extracellular vesicles (EVs) are highly heterogeneous, and different EV subpopulations from various origins mediate different biological effects. The separation of different subpopulations of EVs from mixtures is critical but challenging. Epididymosomes are secreted by the epididymal epithelium and play a key role in sperm maturation and function. However, limited access to human epididymal tissue and epididymal fluid has hampered further study of epididymosomes and their potential clinical applications. Here, we established a novel strategy based on flow cytometry sorting to isolate human CD63-positive epididymosomes from ejaculate. We identified CD52, a membrane-located protein expressed exclusively in the epididymis, as the sorting marker for human epididymosomes. Then, CD63-positive epididymosomes were isolated from human semen using a flow cytometry sorting instrument and concentrated. Additionally, we observed that isolated CD63-positive epididymosomes improved sperm function more than other CD63-positive seminal EV subpopulations did, demonstrating the successful isolation of a subpopulation of epididymosomes from human semen and their potential application in the clinic.
Assuntos
Epididimo , Sêmen , Espermatozoides , Humanos , Masculino , Antígeno CD52/metabolismo , Epididimo/metabolismo , Vesículas Extracelulares/metabolismo , Citometria de Fluxo/métodos , Sêmen/citologia , Sêmen/metabolismo , Espermatozoides/metabolismo , Tetraspanina 30/metabolismoRESUMO
Protein malnutrition during critical periods poses significant risks to reproductive health. Thus, this study aims to evaluate the immediate and delayed effects of a 30-day low-protein diet on the postnatal development of the male reproductive system. For so, male rats were fed a protein-deficient diet from postnatal day 30-60, followed by evaluations of testis, epididymis, and spermatozoa both at the end of the diet and after a 60-day recovery period. Testicular and epididymal weight was lowered in pubertal animals. Several histological alterations were found in the testis, such as acidophilic cells and vacuoles in the seminiferous epithelium, and sperm production was compromised. In the epididymis, the luminal compartment was diminished, and the stroma was enlarged both in the caput and cauda; in the cauda, the epithelial compartment was enlarged; the transit time of spermatozoa through this organ was diminished. Testosterone production was lowered. Spermatozoa's motility, mitochondrial activation, and acrosomal integrity were impaired, and several alterations in morphology were observed. After the recovery period, testicular and epididymal weight was restored. Tissue remodulation was observed in the epididymis, but the spermatozoa's transit time in this organ was not altered. Sperm and testosterone production, spermatozoa motility, mitochondrial activation, and acrosomal integrity were also restored. However, testicular histological alterations and spermatic morphological abnormalities were maintained in protein-restricted animals. Protein restriction during peripuberty impairs the reproductive maturation of pubertal Wistar rats, impairing testicular and epididymal function, with lasting effects even after dietary correction.
Assuntos
Epididimo , Ratos Wistar , Espermatozoides , Testículo , Animais , Masculino , Epididimo/metabolismo , Epididimo/patologia , Testículo/patologia , Testículo/metabolismo , Espermatozoides/patologia , Espermatozoides/metabolismo , Ratos , Dieta com Restrição de Proteínas/efeitos adversos , Maturidade Sexual/fisiologia , Motilidade dos EspermatozoidesRESUMO
J Reprod Dev, Vol. 70, No. 4, p. 255 Table 2 have been corrected. For the bottom of Survived (%) row, the Survived value, which read "69", should be replaced with "86".
Assuntos
Epididimo , Injeções de Esperma Intracitoplásmicas , Espermatozoides , Testículo , Zigoto , Animais , Masculino , Ratos , Epididimo/citologia , Injeções de Esperma Intracitoplásmicas/métodos , Feminino , Desenvolvimento Embrionário/fisiologiaRESUMO
AIM: Obstructive sleep apnea (OSA) is a growing health problem affecting nearly 1 billion people worldwide. The landmark feature of OSA is chronic intermittent hypoxia (CIH), accounting for multiple organ damage, including heart disease. CIH profoundly alters both visceral white adipose tissue (WAT) and heart structure and function, but little is known regarding inter-organ interaction in the context of CIH. We recently showed that visceral WAT senescence drives myocardial alterations in aged mice without CIH. Here, we aimed at investigating whether CIH induces a premature visceral WAT senescent phenotype, triggering subsequent cardiac remodeling. METHODS: In a first experiment, 10-week-old C57bl6J male mice (n = 10/group) were exposed to 14 days of CIH (8 h daily, 5%-21% cyclic inspired oxygen fraction, 60 s per cycle). In a second series, mice were submitted to either epididymal WAT surgical lipectomy or sham surgery before CIH exposure. Finally, we used p53 deficient mice or Wild-type (WT) littermates, also exposed to the same CIH protocol. Epididymal WAT was assessed for fibrosis, DNA damages, oxidative stress, markers of senescence (p16, p21, and p53), and inflammation by RT-qPCR and histology, and myocardium was assessed for fibrosis and cardiomyocyte hypertrophy. RESULTS: CIH-induced epididymal WAT remodeling characterized by increased fibrosis, oxidative stress, DNA damage response, inflammation, and increased expression of senescent markers. CIH-induced epididymal WAT remodeling was associated with subtle and early myocardial interstitial fibrosis. Both epididymal WAT surgical lipectomy and p53 deletion prevented CIH-induced myocardial fibrosis. CONCLUSION: Short-term exposure to CIH induces epididymal WAT senescent remodeling and cardiac interstitial fibrosis, the latter being prevented by lipectomy. This finding strongly suggests visceral WAT senescence as a new target to mitigate OSA-related cardiac disorders.
Assuntos
Tecido Adiposo Branco , Fibrose , Hipóxia , Camundongos Endogâmicos C57BL , Animais , Masculino , Hipóxia/metabolismo , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/patologia , Camundongos , Fibrose/metabolismo , Senescência Celular , Epididimo/metabolismo , Epididimo/patologia , Miocárdio/metabolismo , Miocárdio/patologiaRESUMO
Semen quality and fertility has declined over the last 50 years, corresponding to ever-increasing environmental stressors. However, the cellular mechanisms involved and their impact on sperm functions remain unknown. In a repeated sampling human cohort study, we identify a significant effect of prior perceived stress to increase sperm motility 2-3 months following stress, timing that expands upon our previous studies revealing significant stress-associated changes in sperm RNA important for fertility. We mechanistically examine this post-stress timing in mice using an in vitro stress model in the epididymal epithelial cells responsible for sperm maturation and find 7282 differentially H3K27me3 bound DNA regions involving genes critical for mitochondrial and metabolic pathways. Further, prior stress exposure significantly changes the composition and size of epithelial cell-secreted extracellular vesicles that when incubated with mouse sperm, increase mitochondrial respiration and sperm motility, adding to our prior work showing impacts on embryo development. Together, these studies identify a time-dependent, translational signaling pathway that communicates stress experience to sperm, ultimately affecting reproductive functions.
Assuntos
Mitocôndrias , Motilidade dos Espermatozoides , Espermatozoides , Animais , Masculino , Motilidade dos Espermatozoides/fisiologia , Espermatozoides/metabolismo , Espermatozoides/fisiologia , Humanos , Camundongos , Mitocôndrias/metabolismo , Respiração Celular , Vesículas Extracelulares/metabolismo , Epididimo/metabolismo , Camundongos Endogâmicos C57BL , Estresse Fisiológico , Adulto , Células Epiteliais/metabolismo , Análise do Sêmen , Estudos de CoortesRESUMO
Sperm small RNAs have emerged as important non-genetic contributors to embryogenesis and offspring health. A subset of sperm small RNAs is thought to be acquired during epididymal transit. However, the identity of the specific small RNAs transferred remains unclear. Here, we employ Cre/Lox genetics to generate germline- and epididymal-specific Dgcr8 knockout (KO) mice to investigate the dynamics of sperm microRNAs (miRNAs) and their functions post-fertilization. Testicular sperm from germline Dgcr8 KO mice has reduced levels of 116 miRNAs. Enthrallingly, following epididymal transit, the abundance of 72% of these miRNAs is restored. Conversely, sperm from epididymal Dgcr8 KO mice displayed reduced levels of 27 miRNAs. This loss of epididymal miRNAs in sperm was accompanied by transcriptomic changes in embryos fertilized by this sperm, which was rescued by microinjection of epididymal miRNAs. These findings ultimately demonstrate the acquisition of miRNAs from the soma by sperm during epididymal transit and their subsequent regulation of embryonic gene expression.
Assuntos
Epididimo , Regulação da Expressão Gênica no Desenvolvimento , Camundongos Knockout , MicroRNAs , Espermatozoides , Animais , MicroRNAs/metabolismo , MicroRNAs/genética , Masculino , Epididimo/metabolismo , Espermatozoides/metabolismo , Camundongos , Feminino , Fertilização/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Embrião de Mamíferos/metabolismoRESUMO
Introduction: Epididymal lumen fluids provides a stable microenvironment for sperm maturation. Ca2+ binding protein CABS1 is known to maintain structural integrity of mouse sperm flagella during epididymal transit of sperm. Besides, CABS1 was reported to contain anti-inflammatory peptide sequences and be present in both human saliva and plasma. However, little is known about the role of CABS1 in regulation of the microenvironment of epididymal lumen fluids. Methods: To further confirm the role of CABS1 in epididymis, we identified the expression of CABS1 in epididymal lumen fluids. Moreover, high performance liquid chromatography, coupled with tandem mass spectrometry technique was used to analyze the metabolic profiles and in vivo microperfusion of the cauda epididymis and inductively coupled plasma mass spectrometry (ICP-MS) assays was used to detect the concentration of metal ion of mouse cauda epididymal lumen fluids in CABS1 deficient and normal mice. Results: The results showed that CABS1 is present in epididymal lumen fluids, and the concentration of calcium in epididymal lumen fluids is not changed in Cabs1-/- male mice. Among 34 differential metabolites identified in cauda epididymis, 21 were significantly upregulated while 13 were significantly downregulated in KO cauda epididymis. Pathway analysis identified pyrimidine metabolism, inositol phosphate metabolism, arachidonic acid metabolism, purine metabolism and histidine metabolism as relevant pathways in cauda epididymis. Discussion: The perturbations of mitochondrial dysfunction and inflammation may be the crucial reason for the poor performance of Cabs1-/- sperm.
Assuntos
Epididimo , Metabolômica , Camundongos Knockout , Espermatozoides , Animais , Masculino , Camundongos , Proteínas de Ligação ao Cálcio/metabolismo , Epididimo/metabolismo , Metabolômica/métodos , Camundongos Endogâmicos C57BL , Maturação do Esperma/fisiologia , Espermatozoides/metabolismoRESUMO
The molecular mechanism of sterility in cattleyak is still unresolved. The related factors of infertility in cattleyak were studied by tissue section, SERPINA5 gene cloning and bioinformatics technology. Tissue sections of the epididymis showed poorly structured and disorganized epithelial cells in the corpus of the epididymis compared to the caput of the epididymis, while in the cauda part of the epididymis, the extra basal smooth muscle was thinner, the surface of the epithelial lumen was discontinuous and the epithelium was markedly degenerated. The results of gene cloning showed that the coding sequence (CDS) region of the SERPINA5 gene in cattleyak was 1215 bp in length, encoding a total of 404 amino acids, of which the isoleucine content was the highest, accounting for a total of 49 amino acids (12.1%). The results of real-time fluorescence quantitative PCR (qPCR) showed that the expression of the SERPINA5 gene in the epididymis caput in cattleyak was significantly higher than that in the corpus and cauda (P < 0.05), but there were no significant differences between the corpus and cauda. In the current study, histological and bioinformatics analysis, physicochemical properties, and the expression analysis of the SERPINA5 gene in different regions of the epididymis in cattleyak were carried out to explore the biological complications of cattleyak infertility.
Assuntos
Epididimo , Epididimo/metabolismo , Animais , Bovinos , Masculino , Clonagem Molecular , Regulação da Expressão Gênica , Biologia Computacional/métodos , Expressão Gênica , Serpinas/genética , Serpinas/metabolismoRESUMO
Ruminants are one of the world's economically important species, and their reproductive health is critical to the economic development of the livestock industry. In recent years, research on the relationship between microbiota and reproductive health has received much attention. Microbiota disruption affects the developmental health of the testes and epididymis, the male reproductive organs of the host, which in turn is related to sperm quality. Maintaining a stable microbiota protects the host from pathogens and increases breeding performance, which in turn promotes the economic development of animal husbandry. In addition, the effects and mechanisms of microbiota on reproduction were further explored. These findings support new approaches to improving and managing reproductive health in ruminants through the microbiota and facilitate further systematic exploration of microbiota-mediated reproductive impacts.
Assuntos
Microbiota , Testículo , Animais , Masculino , Testículo/microbiologia , Saúde Reprodutiva , Ruminantes/microbiologia , Reprodução/fisiologia , Epididimo/microbiologia , Espermatozoides/fisiologia , Espermatozoides/microbiologiaRESUMO
The epididymis, a key reproductive organ, is crucial for sperm concentration, maturation, and storage. Despite a comprehensive understanding of many of its functions, several aspects of the complex processes within the epididymis remain obscure. Dysfunction in this organ is intricately connected to the formation of the microenvironment, disruptions in sperm maturation, and the progression of male infertility. Thus, elucidating the functional mechanisms of the epididymal epithelium is imperative. Given the variety of cell types present within the epididymal epithelium, utilizing a three-dimensional (3D) in vitro model provides a holistic and practical framework for exploring the multifaceted roles of the epididymis. Organoid cell culture, involving the co-cultivation of pluripotent or adult stem cells with growth factors on artificial matrix scaffolds, effectively recreates the in vivo cell growth microenvironment, thereby offering a promising avenue for studying the epididymis. The field of epididymal organoids is relatively new, with few studies focusing on their formation and even fewer detailing the generation of organoids that exhibit epididymis-specific structures and functions. Ongoing challenges in both clinical applications and mechanistic studies underscore the importance of this research. This review summarizes the established methodologies for inducing the in vitro cultivation of epididymal cells, outlines the various approaches for the development of epididymal organoids, and explores their potential applications in the field of male reproductive biology.
Assuntos
Epididimo , Organoides , Epididimo/citologia , Epididimo/metabolismo , Organoides/citologia , Organoides/metabolismo , Masculino , Humanos , AnimaisRESUMO
Gut microbiota symbiosis faces enormous challenge with increasing exposure to drugs such as environmental poisons and antibiotics. The gut microbiota is an important component of the host microbiota and has been proven to be involved in regulating spermatogenesis, but the molecular mechanism is still unclear. A male mouse model with gut microbiota depletion/dysbiosis was constructed by adding combined antibiotics to free drinking water, and reproductive parameters such as epididymal sperm count, testicular weight and paraffin sections were measured. Testicular transcriptomic and serum metabolomic analyses were performed to reveal the molecular mechanism of reproductive dysfunction induced by gut microbiota dysbiosis in male mice.This study confirms that antibiotic induced depletion of gut microbiota reduces sperm count in the epididymis and reduces germ cells in the seminiferous tubules in male mice. Further study showed that exosomes isolated from microbiota-depleted mice led to abnormally high levels of retinoic acid and decrease in the number of germ cells in the seminiferous tubules and sperm in the epididymis. Finally, abnormally high levels of retinoic acid was confirmed to disrupted meiotic processes, resulting in spermatogenesis disorders. This study proposed the concept of the gut microbiota-exosome-retinoic acid-testicular axis and demonstrated that depletion of the gut microbiota caused changes in the function of exosomes, which led to abnormal retinoic acid metabolism in the testis, thereby impairing meiosis and spermatogenesis processes.
Assuntos
Disbiose , Exossomos , Microbioma Gastrointestinal , Espermatogênese , Testículo , Tretinoína , Animais , Masculino , Espermatogênese/efeitos dos fármacos , Tretinoína/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Exossomos/metabolismo , Exossomos/efeitos dos fármacos , Camundongos , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testículo/patologia , Disbiose/induzido quimicamente , Antibacterianos/toxicidade , Camundongos Endogâmicos C57BL , Epididimo/efeitos dos fármacos , Epididimo/metabolismo , Epididimo/patologia , Contagem de Espermatozoides , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/patologiaRESUMO
Zinc (Zn) is an essential trace element; it exhibits a plethora of physiological properties and biochemical functions. It plays a pivotal role in regulating the cell cycle, apoptosis, and DNA organization, as well as in protein, lipid, and carbohydrate metabolism. Among other important processes, Zn plays an essential role in reproductive health. The ZIP and ZnT proteins are responsible for the mobilization of Zn within the cell. Zn is an inert antioxidant through its interaction with a variety of proteins and enzymes to regulate the redox system, including metallothioneins (MTs), metalloenzymes, and gene regulatory proteins. The role of Zn in the reproductive system is of great importance; processes, such as spermatogenesis and sperm maturation that occur in the testicle and epididymis, respectively, depend on this element for their development and function. Zn modulates the synthesis of androgens, such as testosterone, for these reproductive processes, so Zn deficiency is related to alterations in sperm parameters that lead to male infertility.
Assuntos
Epididimo , Testículo , Zinco , Masculino , Zinco/metabolismo , Epididimo/metabolismo , Humanos , Testículo/metabolismo , Animais , Espermatogênese , Espermatozoides/metabolismo , Infertilidade Masculina/metabolismo , Maturação do Esperma/fisiologiaRESUMO
Sperm undergo a series of changes in the epididymis region before acquiring the ability to move and fertilize, and the identification of genes expressed in a region-specific manner in the epididymis provides a valuable insight into functional differences between regions. We collected epididymal tissue from three yaks and cultured epithelial cells from the caput, corpus and cauda regions of the yak epididymis using the tissue block method. RNA sequencing analysis (RNA-seq) technology was used to detect gene expression in yak epididymal caput, corpus and cauda epithelial cells. The results showed that the DEGs were highest in the caput vs. corpus comparison, and lowest in the corpus vs. cauda comparison. Six DEGs were verified by real-time fluorescence quantitative PCR (qRT-PCR), consistent with transcriptome sequencing results. The significantly enriched DNA replication pathway in the caput vs. corpus was coordinated with cell proliferation, while upregulated DEGs such as POLD1 and MCM4 were found in the DNA replication pathway. The AMPK signaling pathway was found significantly enriched in the caput vs cauda, suggesting its involvement in sperm maturation and capacitation. The TGF beta signaling pathway was screened in the corpus vs cauda and is crucial for mammalian reproductive regulation. Upregulated DEGs (TGFB3, INHBA, INHBB) are involved in the TGF beta signaling pathway. This study provides a reference for culturing yak epididymal epithelial cells in vitro, and elucidates the transcriptional profiles of epithelial cells in different segments of the epididymis, revealing the regulatory and functional differences between different segments, providing basic data for exploring the molecular mechanism of yak sperm maturation and improving the reproductive capacity of high-altitude mammals.
Assuntos
Epididimo , Células Epiteliais , Animais , Epididimo/metabolismo , Epididimo/citologia , Bovinos/metabolismo , Masculino , Células Epiteliais/metabolismo , Células Epiteliais/citologia , Transcriptoma , Transdução de Sinais , Células Cultivadas , Maturação do Esperma/genética , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/genéticaRESUMO
Aquaporins (AQPs), also known as water channels, appear to be particularly promising in maintaining male reproductive potential. Therefore, this study aimed to determine the presence of classical AQPs in the bovine (Bos taurus) reproductive system and analyze changes in their expression with age using immunohistochemistry and Western blotting. Of the six classical AQPs, AQP0, AQP1, AQP4, AQP5 and AQP6 were detected, while AQP2 was absent. In the testis, AQP0 was visible in Leydig cells in selected animals, while AQP1 was found in myoid cells surrounding the seminiferous tubules of mature individuals. This characteristic expression patterns of AQP0, limited only to certain bulls, is difficult to explain unequivocally. It is possible that AQP0 expression in cattle is subject to individual variability or changes in response to specific physiological conditions. In the caput and corpus epididymis, AQP0 showed weak expression in epithelial cells of immature animals and stronger expression in basal and principal cells of reproductive bulls. In all animals, AQP1 was present on the apical surface of epithelial cells in the initial segment of the caput epididymis. AQP4, AQP5 and AQP6 were identified in principal and basal cells along the entire epididymis of reproductive bulls. The abundance of AQP4 and AQP6 increased from the caput to the cauda epididymis with the growth and development of the animals. In all males, AQP4, AQP5 and AQP6 were observed in epithelial cells of the vas deferens, and their expression in this section increased with age. In conclusion, the abundance and distribution of the classical AQPs in various cell types and parts of the male reproductive system indicate their crucial role in maintaining water homeostasis, which is essential for normal reproductive function in cattle.
Assuntos
Aquaporinas , Animais , Masculino , Bovinos , Aquaporinas/metabolismo , Aquaporinas/genética , Epididimo/metabolismo , Genitália Masculina/metabolismo , Testículo/metabolismo , Imuno-HistoquímicaRESUMO
Background: Oligospermia is one of the most common reasons for male infertility which is troubling numerous couples of child-bearing age. This investigation scrutinizes the implications and mechanistic underpinnings of ursolic acid's effect on busulfan-induced oligospermia in mouse models. Methods: A singular intraperitoneal injection of busulfan at a dosage of 30 mg/kg induced oligospermia. Two weeks subsequent to this induction, mice were subjected to various dosages of ursolic acid (10, 30, and 50 mg/kg body weight, respectively) on a daily basis for four consecutive weeks. Following this treatment period, a meticulous analysis of epididymal sperm parameters, encompassing concentration and motility, was conducted using a computer-assisted sperm analysis system. The histopathology of the mice testes was performed utilizing hematoxylin and eosin staining, and the cytoskeleton regeneration of the testicular tissues was analyzed via immunofluorescent staining. Serum hormone levels, including testosterone, luteinizing hormone, and follicle-stimulating hormone, as well as reactive oxygen species levels (inclusive of reactive oxygen species and malondialdehyde), were gauged employing specific enzyme-linked immunosorbent assay kits. Differentially expressed genes of testicular mRNA between the oligospermia-induced group and the various ursolic acid treatment groups were identified through RNA sequencing analysis. Results: The results revealed that a dosage of 50 mg/kg ursolic acid treatment could increase the concentration of epididymal sperm in oligospermia mice, promote the recovery of testicular morphology, regulate hormone levels and ameliorate oxidative damage. The mechanism research results indicated that ursolic acid increased the expression level of genes related to motor proteins in oligospermia mice.
Assuntos
Bussulfano , Oligospermia , Testículo , Triterpenos , Ácido Ursólico , Animais , Masculino , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Oligospermia/induzido quimicamente , Oligospermia/tratamento farmacológico , Camundongos , Testículo/efeitos dos fármacos , Testículo/patologia , Testículo/metabolismo , Modelos Animais de Doenças , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Espermatozoides/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Testosterona/sangue , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Hormônio Luteinizante/metabolismo , Epididimo/efeitos dos fármacos , Epididimo/patologia , Epididimo/metabolismoRESUMO
Epididymal tuberculosis is rare and often presents diagnostic difficulties. It may be indicative of a disseminated form of the infection, which is the case of our patient. A 19-year-old man, with no past medical history, was admitted for a swollen painful left scrotum that had been evolving for 8 months. He had undergone an orchiectomy and the anatomopathological examination was consistent with epididymal tuberculosis. The radiological investigations had revealed other localizations of the infection: lymphatic, pulmonary, parietal and osteoarticular tuberculosis. Anti-tuberculosis therapy was introduced. However, in the 4th month of treatment, the patient developed seizures. A cerebral magnetic resonance imaging was practiced, concluding to cerebral tuberculomas. Anti-tuberculosis treatment was continued associated to an anticonvulsant with a favourable outcome. The originality of our observation resides in the mode of revelation of a disseminated paucisymptomatic tuberculosis, by an epididymal localization, in an immunocompetent patient.
Assuntos
Antituberculosos , Epididimo , Imunocompetência , Imageamento por Ressonância Magnética , Tuberculose dos Genitais Masculinos , Humanos , Masculino , Adulto Jovem , Antituberculosos/administração & dosagem , Epididimo/patologia , Epididimo/microbiologia , Tuberculose dos Genitais Masculinos/diagnóstico , Tuberculose dos Genitais Masculinos/tratamento farmacológico , Orquiectomia , Convulsões/etiologia , Anticonvulsivantes/administração & dosagem , Tuberculoma Intracraniano/diagnóstico , Tuberculoma Intracraniano/tratamento farmacológicoRESUMO
The sperm-associated antigen 11a (Spag11a) gene is exclusively expressed in the caput epididymis. Our previous studies demonstrated that small interfering RNA (siRNA)-mediated ablation of this gene resulted in increased proliferation of epididymal epithelial cells. Further, active immunization-mediated ablation of SPAG11A protein increased the susceptibility of male reproductive tract tissues to diethylnitrosamine (DEN)-induced tumorigenesis. In this study, we report that the caput epididymis of Spag11a knockout mice displayed hyperplasia and inflammation, while the caput epididymis of wild-type mice exhibited normal anatomical structure. Global transcriptome analyses in the caput epididymis of knockout mice indicated differential expression of genes involved in a variety of cellular processes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses suggested that the absence of Spag11a may activate microRNAs associated with cancer, chemical carcinogenesis-receptor activation, and chemical carcinogenesis-DNA adducts pathways; which may contribute to the promotion of tumorigenesis in the epididymis. The susceptibility of caput epididymis to chemically induced carcinogenesis in Spag11a knockout mice was analyzed. Histological analyses indicated that while the epididymis of wild-type mice did not show any signs of tumorigenesis, knockout mice displayed hyperplasia, anaplasia, dysplasia, neoplasia, and inflammation in the caput epididymis. Our results provide concrete evidence that deletion of Spag11a induces histopathological and molecular changes that contribute to tumorigenesis. It is possible that the expression of Spag11a gene could be one of the reasons for the rarity of epididymal cancers. The involvement of an epididymal gene in tumorigenesis is being demonstrated for the first time.
Assuntos
Epididimo , Camundongos Knockout , Animais , Masculino , Epididimo/patologia , Epididimo/metabolismo , Camundongos , Camundongos Endogâmicos C57BLRESUMO
The scenario of the fertile spermatozoa with high fertilizing capability is basically dependent on gene expression-based epididymal function. The current investigation aimed to declare the varied expression of different candidate genes (PLA2G4D, LCN15, CLUAP1, SPP1, AQP12B, DEFB110 and ESR1) relevant to spermatozoa features between the different epididymal segments in the mature dromedary camels (n = 30). Scrotal contents were collected post-slaughtering, during the breeding season and the epididymis was separated from the testicles and divided into three segments (caput, corpus and cauda) based on its morphology and anatomical characteristics. Epididymal spermatozoa were harvested from each epididymal portion and evaluated for motility, count, viability and morphology. Samples were grouped depending on their epididymal sperm cells features into high-fertile (n = 15) and low-fertile (n = 15) groups. The gene expression of the candidate genes was defined in the isolated RNA from each epididymal portion tissue. The segmental sperm motion and count were significantly (p < .05 and p < .01) higher in the three epididymal parts of high-fertile camels than the lower ones. There were some candidate genes markedly up-regulated in its expression in epididymal head of high-fertile camels (PLA2G4D and LCN15) and low fertile (CLUAP1), while others in the body region of the high-fertile group (SPP1, AQP12B and DEFB110). Nevertheless, ER1 did not differ in the expression among the epididymal segments. In conclusion, the variant expression patterns of these epididymal genes in relation to the regional spermatozoa features might suggest important roles of these genes in sperm maturation process in the epididymis and focusing more interest on their potential utility as markers for male camel fertility prediction.