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Animals : An Open Access Journal From... May 2024We identified Wdr17 as a highly expressed gene in pachytene spermatocytes by transcriptomic analysis of mouse testis. Germ cell-deficient infertile mouse models had...
We identified Wdr17 as a highly expressed gene in pachytene spermatocytes by transcriptomic analysis of mouse testis. Germ cell-deficient infertile mouse models had significantly reduced Wdr17 expression. We performed gene interference and overexpression in the mouse spermatocyte cell line GC-2spd(ts) and investigated how Wdr17 affects spermatocyte growth and development. Our results showed that Wdr17 suppression significantly decreased cell growth rate and increased cell apoptosis in GC-2spd(ts) cells. Wdr17 suppression also arrested the cell cycle at the G1 phase. On the contrary, Wdr17 overexpression significantly promoted cell proliferation and inhibited cell apoptosis in GC-2spd(ts) cells. More cells were enriched at the S stage with a concomitant reduction of cells at the G1 stage. Wdr17 promotes mouse spermatocyte proliferation by advancing cell cycle progression and inhibiting cell apoptosis, indicating its potential role in regulating spermatogenesis in the mouse.
PubMed: 38791636
DOI: 10.3390/ani14101418 -
Animals : An Open Access Journal From... May 2024Aberrant expression of the heat shock proteins and factors was revealed to be closely associated with male reproduction. Heat shock factor 2 (HSF2) is a transcription...
Aberrant expression of the heat shock proteins and factors was revealed to be closely associated with male reproduction. Heat shock factor 2 (HSF2) is a transcription factor that is involved in the regulation of diverse developmental pathways. However, the role and the corresponding molecular mechanism of in male cattle-yak sterility are still poorly understood. Therefore, the aim of this study was to obtain the sequence and the biological information of the cattle-yak gene and to investigate the spatiotemporal expression profiles of the locus during the development of cattle-yak testes. Additionally, the differential expression was analyzed between the cattle-yak and the yak, and the methylation of corresponding promoter regions was compared. Our results showed an additional 54 bp fragment and a missense mutation (lysine to glutamic acid) were presented in the cattle-yak gene, which correlated with enriched expression in testicular tissue. In addition, the expression of the gene showed dynamic changes during the growth of the testes, reaching a peak in adulthood. The IHC indicated that HSF2 protein was primarily located in spermatocytes (PS), spermatogonia (SP), and Sertoli cells (SC) in cattle-yak testes, compared with the corresponding cells of cattle and the yak. Furthermore, bisulfite-sequencing PCR (BSP) revealed that the methylated CpG sites in the promoter region of the cattle-yak HSF2 were more numerous than in the yak counterpart, which suggests hypermethylation of this region in the cattle-yak. Taken together, the low expression abundance and hypermethylation of may underpin the obstruction of spermatogenesis, which leads to male cattle-yak infertility. Our study provided a basic guideline for the gene in male reproduction and a new insight into the mechanisms of male cattle-yak sterility.
PubMed: 38791628
DOI: 10.3390/ani14101410 -
Antioxidants (Basel, Switzerland) Apr 2024Redox balance plays an important role in testicular homeostasis. While lots of antioxidant molecules have been identified as widely expressed, the understanding of the...
Redox balance plays an important role in testicular homeostasis. While lots of antioxidant molecules have been identified as widely expressed, the understanding of the critical mechanisms for redox management in male germ cells is inadequate. This study identified LanCL2 as a major male germ cell-specific antioxidant gene that is important for testicular homeostasis. Highly expressed in the brain and testis, LanCL2 expression correlates with testicular maturation and brain development. LanCL2 is enriched in spermatocytes and round spermatids of the testis. By examining LanCL2 knockout mice, we found that LanCL2 deletion did not affect postnatal brain development but injured the sperm parameters of adult mice. With histopathological analysis, we noticed that LanCL2 KO caused a pre-maturation and accelerated the self-renewal of spermatogonial stem cells in the early stage of spermatogenesis. In contrast, at the adult stage, LanCL2 KO damaged the acrosomal maturation in spermiogenesis, resulting in spermatogenic defects with a reduced number and motility of spermatozoa. Furthermore, we show that this disruption of testicular homeostasis in the LanCL2 KO testis was due to dysbalanced testicular redox homeostasis. This study demonstrates the critical role of LanCL2 in testicular homeostasis and redox balance.
PubMed: 38790639
DOI: 10.3390/antiox13050534 -
Human Pathology Jun 2024Spermatocytic tumors are rare testicular tumors occurring predominantly in older men. Most show a classical tripartite morphology (different from seminoma) and are...
Spermatocytic tumors are rare testicular tumors occurring predominantly in older men. Most show a classical tripartite morphology (different from seminoma) and are benign. However, well-documented cases of malignant spermatocytic tumors exist. Our previous work showed that a subset of spermatocytic tumors exhibiting TP53 mutations, DNA methylation profiles closer to seminomas, and/or gains in chromosome 12p exhibited aggressive characteristics, including sarcomatoid transformation and metastatic dissemination. The microRNA-371-373 cluster is a promising biomarker which is upregulated in non-teratoma germ cell tumors with malignant behavior. In this work we analyze microRNAs-371-373 b y quantitative real-time polymerase chain reaction in 18 spermatocytic tumors representative of the whole clinical spectrum, including 6 with aggressive features (sarcomatoid transformation, metastases, or gains in chromosome 12p). The levels of microRNAs-371-373 were significantly higher in non-teratoma germ cell tumors compared to spermatocytic tumors, overall (p < 0.0001). Importantly, levels of microRNA-371-373 were higher in spermatocytic tumors with aggressive features compared to non-aggressive neoplasms. The highest levels were observed in one tumor showing isochromosome 12p. These results further support our previous findings that a subset of spermatocytic tumors are intermediate between so-called type II and type III germ cell tumors and that embryonic microRNAs play a role in aggressive behavior in spermatocytic tumors. Accordingly, this subset of tumors may behave aggressively and require close follow up. In the future, this opens an opportunity for microRNA testing in serum of spermatocytic tumor patients for risk stratification purposes.
Topics: Humans; Male; MicroRNAs; Testicular Neoplasms; Neoplasms, Germ Cell and Embryonal; Adult; Biomarkers, Tumor; Middle Aged; Aged; Real-Time Polymerase Chain Reaction; Gene Expression Regulation, Neoplastic; Young Adult
PubMed: 38782099
DOI: 10.1016/j.humpath.2024.05.005 -
BMC Complementary Medicine and Therapies May 2024This study investigated the effect of curcumin nanomicelle (CUR-n) on the structure of testis tissue, the process of spermatogenesis, LH, FSH, testosterone, and...
BACKGROUND
This study investigated the effect of curcumin nanomicelle (CUR-n) on the structure of testis tissue, the process of spermatogenesis, LH, FSH, testosterone, and oxidative stress in a model of multiple sclerosis.
METHODS
Twenty-four male mice C57BL/6 were randomly allocated into 4 groups of 6 (1: group receiving 2% CPZ diet, 2: group receiving the diet of 2% CPZ + CUR-n with a dose of 50 mg/kg, 3: group receiving the diet of 2% CPZ + CUR-n with a dose of 100 mg/kg). The concentration of hormones (testosterone, LH and FSH), was measured by the special hormone assay ELISA kits. Measuring total antioxidant capacity (TAC) and Malondialdehyde (MDA) levels was done by spectrophotometry and calorimetric methods, respectively. Stereological analysis was done in order to explore the number of spermatogenesis cells, testis and sperm properties.
RESULTS
The results indicated that CUR-n (100 mg/kg) significantly enhanced the concentration of LH, FSH, testosterone, and TAC but reduced MDA levels. It also notably increased the quantity of spermatogonia, spermatocyte, round spermatids, long spermatids and LCs, augmented testis weight and volume, and germinal epithelium volume, improved sperm count, morphology, viability, and motility. In addition, a considerable decrease in the amount of wrinkling and disruption of the germinal epithelium was observed after intervention with CUR-n (100 mg/kg). Furthermore, a significant increase in the number of germ cells compared to the group receiving CPZ was detected.
CONCLUSION
This study proposes that CUR-n could be a therapeutic agent for decreasing the adverse effects of MS on testis.
Topics: Male; Animals; Curcumin; Mice; Testis; Disease Models, Animal; Mice, Inbred C57BL; Multiple Sclerosis; Spermatogenesis; Testosterone; Oxidative Stress; Micelles
PubMed: 38778296
DOI: 10.1186/s12906-024-04423-3 -
Zoological Research May 2024Meiosis is a highly complex process significantly influenced by transcriptional regulation. However, studies on the mechanisms that govern transcriptomic changes during...
Meiosis is a highly complex process significantly influenced by transcriptional regulation. However, studies on the mechanisms that govern transcriptomic changes during meiosis, especially in prophase I, are limited. Here, we performed single-cell ATAC-seq of human testis tissues and observed reprogramming during the transition from zygotene to pachytene spermatocytes. This event, conserved in mice, involved the deactivation of genes associated with meiosis after reprogramming and the activation of those related to spermatogenesis before their functional onset. Furthermore, we identified 282 transcriptional regulators (TRs) that underwent activation or deactivation subsequent to this process. Evidence suggested that physical contact signals from Sertoli cells may regulate these TRs in spermatocytes, while secreted ENHO signals may alter metabolic patterns in these cells. Our results further indicated that defective transcriptional reprogramming may be associated with non-obstructive azoospermia (NOA). This study revealed the importance of both physical contact and secreted signals between Sertoli cells and germ cells in meiotic progression.
Topics: Animals; Male; Mice; Meiosis; Humans; Cell Communication; Sertoli Cells; Testis; Spermatogenesis; Gene Expression Regulation; Azoospermia; Transcription, Genetic; RNA, Small Cytoplasmic; Single-Cell Gene Expression Analysis
PubMed: 38766744
DOI: 10.24272/j.issn.2095-8137.2023.414 -
American Journal of Human Genetics Jun 2024Sperm production and function require the correct establishment of DNA methylation patterns in the germline. Here, we examined the genome-wide DNA methylation changes...
Sperm production and function require the correct establishment of DNA methylation patterns in the germline. Here, we examined the genome-wide DNA methylation changes during human spermatogenesis and its alterations in disturbed spermatogenesis. We found that spermatogenesis is associated with remodeling of the methylome, comprising a global decline in DNA methylation in primary spermatocytes followed by selective remethylation, resulting in a spermatids/sperm-specific methylome. Hypomethylated regions in spermatids/sperm were enriched in specific transcription factor binding sites for DMRT and SOX family members and spermatid-specific genes. Intriguingly, while SINEs displayed differential methylation throughout spermatogenesis, LINEs appeared to be protected from changes in DNA methylation. In disturbed spermatogenesis, germ cells exhibited considerable DNA methylation changes, which were significantly enriched at transposable elements and genes involved in spermatogenesis. We detected hypomethylation in SVA and L1HS in disturbed spermatogenesis, suggesting an association between the abnormal programming of these regions and failure of germ cells progressing beyond meiosis.
Topics: Humans; Spermatogenesis; Male; DNA Methylation; Genome, Human; Spermatids; Spermatocytes; DNA Transposable Elements; Spermatozoa; Meiosis; Transcription Factors
PubMed: 38759652
DOI: 10.1016/j.ajhg.2024.04.017 -
Frontiers in Microbiology 2024Cryopreservation of semen can give full play to the reproductive advantages of male animals. However, in actual production, due to the poor frost resistance of sheep...
INTRODUCTION
Cryopreservation of semen can give full play to the reproductive advantages of male animals. However, in actual production, due to the poor frost resistance of sheep semen and the low conception rate, the promotion of sheep frozen semen is greatly hindered. Therefore, it is urgent to improve the frost resistance of semen to improve the quality of frozen semen. At present, most studies on improving the quality of frozen semen are based on the improvement of semen dilutions, and few studies on improving the freezing resistance of ram semen by feeding functional amino acids.
METHODS
Therefore, 24 Turpan black rams were divided into high antifreeze group (HF) and a low antifreeze group (LF) Each of these groups was further randomly divided into control and experimental subgroups. The control subgroup was fed a basal diet, while the experimental subgroup received an additional 12 g/d of -Cit supplementation based on the control group for a duration of 90 days.
RESULTS
The results showed that Following -Cit supplementation, the experimental group demonstrated significantly elevated sperm density and VSL (Velocity of straight line), T-AOC, GSH-Px, and NO levels in fresh semen compared to the control group ( < 0.01). After thawing, the experimental group exhibited significantly higher levels of T-AOC, GSH-Px, and NO compared to the control group ( < 0.01). Additionally, the HFT group, after thawing frozen semen, displayed significantly higher HK1 protein expression compared to the control group. The number of spermatogonia, spermatocytes, and sperm cells in the HFT group was significantly higher than that in the HFC group. Moreover, 16S rRNA sequence analysis showed that , and were significantly enriched in the rumen of the HFT group, while was significantly enriched in the HFC group. In the duodenum, , and were significantly enriched in the HFT group, whereas and were significantly enriched in the HFC group.
DISCUSSION
Under the conditions employed in this study, -Cit supplementation was found to enhance the intestinal flora composition in rams, thereby improving semen quality, enhancing the antifreeze performance of semen, and promoting the development of testicular spermatogenic cells.
PubMed: 38756735
DOI: 10.3389/fmicb.2024.1396796 -
Frontiers in Veterinary Science 2024This study aimed to explore the effects of neonatal vitamin A (VA) supplementation on testis development and spermatogenesis. A total of 32 newborn lambs were...
This study aimed to explore the effects of neonatal vitamin A (VA) supplementation on testis development and spermatogenesis. A total of 32 newborn lambs were intramuscularly injected with corn oil (control group) or corn oil + 2500 IU/kg BW VA (VA group). They were slaughtered and sampled at 3 weeks and 8 months of age to analyze spermatogenesis, cell proliferation, hormone secretion, antioxidant status of the testis, and adult sheep sperm parameters. Compared with the control group, the expression of spermatogonial differentiation-related genes in VA group was up-regulated ( < 0.05). Testis weight, seminiferous tubule diameter, number of spermatogonium and spermatocyte, and sperm density increased significantly in VA group at 8 months of age ( < 0.05). Neonatal VA injection upregulated the expression of the cell proliferation marker and cell cycle-related genes in the testis ( < 0.05). VA increased the concentrations of testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in the serum and upregulated steroidogenesis-related genes in the testis ( < 0.05). The antioxidant levels in the VA group were maintained at high levels. The total antioxidant capacity (T-AOC), antioxidant enzyme content and antioxidant-related genes were increased in the testis ( < 0.05). Furthermore, neonatal VA injection activated retinoic acid (RA) signaling to maintain the blood-testosterone barrier (BTB) in the testis of 3-week-old sheep. AMP-activated protein kinase (AMPK) and protein kinase B (AKT) signaling were also modulated in the sheep testis ( < 0.05). Taken together, VA supplementation in newborn rams promotes testis development and spermatogenesis to improve fertility.
PubMed: 38756517
DOI: 10.3389/fvets.2024.1370576 -
PloS One 2024Calcium binding protein, spermatid associated 1 (CABS1) is a protein most widely studied in spermatogenesis. However, mRNA for CABS1 has been found in numerous tissues,...
Calcium binding protein, spermatid associated 1 (CABS1) is a protein most widely studied in spermatogenesis. However, mRNA for CABS1 has been found in numerous tissues, albeit with little information about the protein. Previously, we identified CABS1 mRNA and protein in human salivary glands and provided evidence that in humans CABS1 contains a heptapeptide near its carboxyl terminus that has anti-inflammatory activities. Moreover, levels of an immunoreactive form of CABS1 were elevated in psychological stress. To more fully characterize human CABS1 we developed additional polyclonal and monoclonal antibodies to different sections of the protein and used these antibodies to characterize CABS1 in an overexpression cell lysate, human salivary glands, saliva, serum and testes using western blot, immunohistochemistry and bioinformatics approaches exploiting the Gene Expression Omnibus (GEO) database. CABS1 appears to have multiple molecular weight forms, consistent with its recognition as a structurally disordered protein, a protein with structural plasticity. Interestingly, in human testes, its cellular distribution differs from that in rodents and pigs, and includes Leydig cells, primary spermatogonia, Sertoli cells and developing spermatocytes and spermatids, Geodata suggests that CABS1 is much more widely distributed than previously recognized, including in the urogenital, gastrointestinal and respiratory tracts, as well as in the nervous system, immune system and other tissues. Much remains to be learned about this intriguing protein.
Topics: Humans; Male; Testis; Calcium-Binding Proteins; Animals; Saliva; Salivary Glands; Spermatids; Spermatogenesis
PubMed: 38753592
DOI: 10.1371/journal.pone.0301855