The association between long noncoding RNA ABHD11-AS1 and malignancy prognosis: a meta-analysis.

BACKGROUND: Accumulating evidence has highlighted that lncRNA ABHD11-AS1 plays an essential role in tumorigenesis and is expected to become a new predictive biomarker and ideal target for cancer therapy, whereas some of their findings are conflicting due to the relatively small sample size of individual studies. Thus, this meta-analysis aimed to quantitatively ascertain the association of ABHD11-AS1 with diverse human malignancies. METHODS: Eight databases were comprehensively screened for relevant articles on January 1, 2024. The significance of ABHD11-AS1 in malignancies was determined by odds ratios (ORs) or hazard ratios (HRs) with corresponding 95% confidence interval (CI). Subgroup analyses and sensitivity analyses were applied to verify the reliability and robustness of the pooled results. Simultaneously, the GEPIA2021 and UCSC Xena databases were applied to further strengthen the results. RESULTS: Fourteen clinical studies comprising eight kinds of malignancies and 1215 malignancy cases were enrolled into this meta-analysis. The pooled results showed that increased ABHD11-AS1 expression was remarkably associated with lymph node metastasis (OR = 2.73, 95%CI [1.97, 3.77], I2 = 0%, p < 0.00001), advanced tumor stage ( OR = 3.14, 95%CI [2.34, 4.21], I2 = 39%, p < 0.00001), and unfavorable overall survival (OS) (HR = 1.81, 95%CI [1.58, 2.06], I2 = 0%, p < 0.00001). Subgroup analyses and sensitivity analyses indicated that the pooled results were reliable and robust. Additionally, ABHD11-AS1 was significantly increased in eight kinds of malignancies according to the validation of the GEPIA2021 database. Meanwhile, the UCSC Xena databases further revealed that elevated ABHD11-AS1 expression was significantly associated with poor prognosis as assessed by progression free interval (PFI), disease free interval (DFI), disease specific survival (DSS), and OS. CONCLUSIONS: Current evidence supports the association of elevated ABHD11-AS1 expression with poor prognosis. Thereby, ABHD11-AS1 may be considered as a promising biomarker to screen cancer and predict malignancy prognosis. Also, there is a necessity for larger-scale multicenter studies with uniform study protocols from different countries to further validate the conclusions.

The prognostic significance of lncRNA FGD5-AS1 in various malignancies: a meta-analysis.

Background: Cancer is widely recognized as a prominent contributor to global mortality due to factors such as delayed diagnosis, unfavorable prognosis, and high likelihood of recurrence. FGD5 transcription factor G antisense RNA 1(FGD5-AS1), a newly identified long non-coding RNA, has emerged as a promising prognostic biomarker, for malignancy prognosis. This meta-analysis aimed to assess the prognostic significance of FGD5-AS1 in various carcinomas. Methods: A systematic search was performed through five electronic databases to identify studies that investigating the role of FGD5-AS1 expression as a prognostic factor in carcinomas. The value of FGD5-AS1 in malignancies was estimated by odds ratios (ORs) and hazard ratios (HRs) with a corresponding 95% confidence intervals (CIs). Furthermore, the GEPIA database was used to further supplement our results. Results: This analysis included 12 studies with 642 cases covering eight cancer types. High FGD5-AS1 expression exhibited a significant correlation with poor overall survival(OS) (HR = 2.04, 95%CI [1.72, 2.42], P < 0.00001), advanced tumor stage (OR = 3.47, 95%CI [2.34, 5.14], P < 0.00001), lymph node metastasis(LNM) (OR = 1.79, 95% CI [1.20,2.67], P = 0.004), and larger tumor size (OR= 5.25, 95%CI [2.68, 10.30], P < 0.00001). Furthermore, the FGD5-AS1 expression was notably upregulated in six types of malignancies as verified using the GEPIA online gene analysis tool. Conclusions: The findings of this meta-analysis indicated that high FGD5-AS1 expression was significantly associated with poor prognosis in diverse cancer types, suggesting that FGD5-AS1 may be a promising biomarker for predicting cancer prognosis. Systematic review registration: https://www.york.ac.uk/inst/crd, identifier CRD42024552582.

Synthesis of a Sodium-Ion Cathode Material Na3Fe2(SO4)3F with the Help of Fluorine Element.

The development of cathode materials has always been one of the most crucial areas of research in the field of sodium-ion batteries. Sulfate-based polyanionic materials, known for their high working voltage characteristics, have received widespread attention. In this work, a fluoro-sulfate sodium-ion battery cathode material, Na3Fe2(SO4)3F modified with carbon nanotubes, was developed using a low-temperature solid-state annealing method. This Na3Fe2(SO4)3F cathode exhibits an exceptionally high voltage of 3.77 V, excellent discharge capacity (102 mAh/g at 0.1C), and good rate capability. This material broadens the research directions for cathode materials and holds promise as a foundation for the further development of high-performance sodium-ion batteries.

A single-cell transcriptomic dataset of pluripotent stem cell-derived astrocytes via NFIB/SOX9 overexpression.

Astrocytes, the predominant glial cells in the central nervous system, play essential roles in maintaining brain function. Reprogramming induced pluripotent stem cells (iPSCs) to become astrocytes through overexpression of the transcription factors, NFIB and SOX9, is a rapid and efficient approach for studying human neurological diseases and identifying therapeutic targets. However, the precise differentiation path and molecular signatures of induced astrocytes remain incompletely understood. Accordingly, we performed single-cell RNA sequencing analysis on 64,736 cells to establish a comprehensive atlas of NFIB/SOX9-directed astrocyte differentiation from human iPSCs. Our dataset provides detailed information about the path of astrocyte differentiation, highlighting the stepwise molecular changes that occur throughout the differentiation process. This dataset serves as a valuable reference for dissecting uncharacterized transcriptomic features of NFIB/SOX9-induced astrocytes and investigating lineage progression during astrocyte differentiation. Moreover, these findings pave the way for future studies on neurological diseases using the NFIB/SOX9-induced astrocyte model.

Modified creatinine index for predicting prognosis in hemodialysis patients: a systematic review and meta-analysis.

BACKGROUND: Currently, several studies have explored the association between the modified creatinine index (mCI) and prognosis in patients on hemodialysis (HD). However, some of their results are contradictory. Therefore, this study was conducted to comprehensively assess the role of mCI in predicting prognosis in HD patients through meta-analysis. METHODS: We searched and screened literature from PubMed, Embase, Web of Science, and Cochrane databases from their establishment until March 2024. Relevant data were extracted. The statistical analysis was performed using Stata 15.0, RevMan 5.4, and Meta DiSc 1.4 software. RESULTS: The results showed a positive association between mCI and nutritional status in HD patients (BMI r = 0.19, 95% CI: 0.1-0.28, p = .000; albumin r = 0.36, 95% CI: 0.33-0.39, p = .000; normalized protein catabolic rate (nPCR) r = 0.25, 95% CI: 0.13-0.38, p = .000). In addition, mCI in deceased HD patients was significantly lower than that in HD survivors (SMD = -0.94, 95% CI: -1.46 to -0.42, p = .000). A low mCI was associated with an increased risk of all-cause death in HD patients (HR = 1.95, 95% CI: 1.57-2.42, p = .000). In addition, a low mCI was significantly associated with decreased overall survival (OS) in HD patients (HR = 3.01, 95% CI: 2.44-3.70, p = .000). mCI showed moderate diagnostic accuracy for sarcopenia in both male and female HD patients (male AUC = 0.7891; female AUC = 0.759). CONCLUSIONS: The mCI can be used as a prognostic marker for HD patients, and monitoring mCI may help to optimize the management of HD and improve overall prognosis in patients.

Total Syntheses and Stereochemical Assignment of Acremolides A and B.

The absolute stereochemical configurations of acremolides A and B were predicted by a biochemistry-based rule and unambiguously confirmed through their total syntheses. The features of the total syntheses include sequential Krische's Ir-catalyzed crotylation, Brown's borane-mediated crotylation, Mitsunobu esterification reaction, and cross-metathesis reaction. The efficient total synthesis enabled clear validation of the predicted stereochemistry for acremolides A and B.

Development and validation of prognostic signatures of NAD+ metabolism and immune-related genes in colorectal cancer.

Background: Colorectal cancer (CRC) is a prevalent cause of death from malignant tumors. This study aimed to develop a nicotinamide adenine dinucleotide (NAD+) metabolism and immune-related prognostic signature, providing a theoretical foundation for prognosis and therapy in CRC patients. Methods: NAD + metabolism-related and immune-related subtypes of CRC patients were identified by consistent clustering. Differentially expressed genes (DEGs) between the two subtypes of CRC were identified by overlapping. A risk signature was constructed using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. Independent prognostic predictors were authenticated by Cox analysis. Gene set variation analysis (GSVA) and single-sample gene set enrichment analysis (ssGSEA) were applied to investigate the connection between the prognostic signature and the immune microenvironment. Chemotherapy drug sensitivity and immunotherapy responsiveness were projected using the 'pRRophetic' package and Tumor Immune Dysfunction and Exclusion (TIDE) website. The Human Protein Atlas (HPA) database was used to assess the protein expression of prognostic genes in CRC and normal tissues. Results: Using bioinformatics methods, three prognostic genes related to immune-related NAD + metabolism were identified, and the results were used to establish and verify a prognostic signature related to immune-related NAD + metabolism in CRC patients. Cox regression analysis confirmed that the risk score was a reliable independent prognostic predictor. GSVA and ssGSEA indicated that the prognostic signature was associated with the immune microenvironment. TIDE analysis suggested that the signature might act as an immunotherapy predictor. Chemotherapy sensitivity analysis revealed that COMP was correlated with chemotherapy sensitivity in CRC patients and might be a potential therapeutic target. Conclusion: This study identified NAD + metabolism-immune-related prognostic genes (MOGAT2, COMP, and DNASE1L3) and developed a prognostic signature for CRC prognosis, which is significant for clinical prognosis prediction and treatment strategy decisions for CRC patients.

Dermal Injection of Recombinant Filaggrin-2 Ameliorates UVB-Induced Epidermal Barrier Dysfunction and Photoaging.

The epidermal barrier is vital for protecting the skin from environmental stressors and ultraviolet (UV) radiation. Filaggrin-2 (FLG2), a critical protein in the stratum corneum, plays a significant role in maintaining skin barrier homeostasis. However, the precise role of FLG2 in mitigating the adverse effects of UV-induced barrier disruption and photoaging remains poorly understood. In this study, we revealed that UVB exposure resulted in a decreased expression of FLG2 in HaCaT keratinocytes, which correlated with a compromised barrier function. The administration of recombinant filaggrin-2 (rFLG2) enhanced keratinocyte differentiation, bolstered barrier integrity, and offered protection against apoptosis and oxidative stress induced by UVB irradiation. Furthermore, in a UV-induced photodamage murine model, the dermal injection of rFLG2 facilitated the enhanced restoration of the epidermal barrier, decreased oxidative stress and inflammation, and mitigated the collagen degradation that is typical of photoaging. Collectively, our findings suggested that targeting FLG2 could be a strategic approach to prevent and treat skin barrier dysfunction and combat the aging effects associated with photoaging. rFLG2 emerges as a potentially viable therapy for maintaining skin health and preventing skin aging processes amplified by photodamage.

Quantitative measurement of cation-mediated adhesion of DNA to anionic surfaces.

Anionic polyelectrolytes, such as DNA, are attracted to anionic surfaces in the presence of multivalent cations. A major barrier toward molecular-level understanding of these attractive interactions is the paucity of measurements of the binding strength. Here, atomic force microscopy-based single molecule force spectroscopy was used to quantify the binding free energy of double-stranded DNA to an anionic surface, with complementary density functional theory calculations of the binding energies of metal ion-ligand complexes. The results support both electrostatic attraction and ion-specific binding. Our study suggests that the correlated interactions between counterions are responsible for attraction between DNA and an anionic surface, but the strength of this attraction is modulated by the identity of the metal ion. We propose a mechanism in which the strength of metal-ligand binding, as well as the preference for particular binding sites, influence both the concentration dependence and the strength of the DNA-surface interactions.

Exploring the potential of machine learning to understand the occurrence and health risks of haloacetic acids in a drinking water distribution system.

Determining the occurrence of disinfection byproducts (DBPs) in drinking water distribution system (DWDS) remains challenging. Predicting DBPs using readily available water quality parameters can help to understand DBPs associated risks and capture the complex interrelationships between water quality and DBP occurrence. In this study, we collected drinking water samples from a distribution network throughout a year and measured the related water quality parameters (WQPs) and haloacetic acids (HAAs). 12 machine learning (ML) algorithms were evaluated. Random Forest (RF) achieved the best performance (i.e., R2 of 0.78 and RMSE of 7.74) for predicting HAAs concentration. Instead of using cytotoxicity or genotoxicity separately as the surrogate for evaluating toxicity associated with HAAs, we created a health risk index (HRI) that was calculated as the sum of cytotoxicity and genotoxicity of HAAs following the widely used Tic-Tox approach. Similarly, ML models were developed to predict the HRI, and RF model was found to perform the best, obtaining R2 of 0.69 and RMSE of 0.38. To further explore advanced ML approaches, we developed 3 models using uncertainty-based active learning. Our findings revealed that Categorical Boosting Regression (CAT) model developed through active learning substantially outperformed other models, achieving R2 of 0.87 and 0.82 for predicting concentration and the HRI, respectively. Feature importance analysis with the CAT model revealed that temperature, ions (e.g., chloride and nitrate), and DOC concentration in the distribution network had a significant impact on the occurrence of HAAs. Meanwhile, chloride ion, pH, ORP, and free chlorine were found as the most important features for HRI prediction. This study demonstrates that ML has the potential in the prediction of HAA occurrence and toxicity. By identifying key WQPs impacting HAA occurrence and toxicity, this research offers valuable insights for targeted DBP mitigation strategies.

Formation of Linear Plasmonic Heterotrimers Using Nanoparticle Docking to DNA Origami Cages.

The fabrication of complex assemblies with interesting collective properties from plasmonic nanoparticles (NPs) is often challenging. While DNA-directed self-assembly has emerged as one of the most promising approaches to forming such complex assemblies, the resulting structures tend to have large variability in gap sizes and shapes, as the DNA strands used to organize these particles are flexible, and the polydispersity of the NPs leads to variability in these critical structural features. Here, we use a new strategy termed docking to DNA origami cages (D-DOC) to organize spherical NPs into a linear heterotrimer with a precisely defined geometrical arrangement. Instead of binding NPs to the exterior of the DNA templates, D-DOC binds the NPs to either the interior or the opening of a 3D cage, which significantly reduces the variability of critical structural features by incorporating multiple diametrically arranged capture strands to tether NPs. Additionally, such a spatial arrangement of the capture strand can work synergistically with shape complementarity to achieve tighter confinement. To assemble NPs via D-DOC, we developed a multistep assembly process that first encapsulates an NP inside a cage and then binds two other NPs to the openings. Microscopic characterization shows low variability in the bond angles and gap sizes. Both UV-vis absorption and surface-enhanced Raman scattering (SERS) measurements showed strong plasmonic coupling that aligned with predictions by electrodynamic simulations, further confirming the precision of the assembly. These results suggest D-DOC could open new opportunities in biomolecular sensing, SERS and fluorescence spectroscopies, and energy harvesting through the self-assembly of NPs into more complex 3D assemblies.

Early blood immune molecular alterations in cynomolgus monkeys with a PSEN1 mutation causing familial Alzheimer's disease.

INTRODUCTION: More robust non-human primate models of Alzheimer's disease (AD) will provide new opportunities to better understand the pathogenesis and progression of AD. METHODS: We designed a CRISPR/Cas9 system to achieve precise genomic deletion of exon 9 in cynomolgus monkeys using two guide RNAs targeting the 3' and 5' intron sequences of PSEN1 exon 9. We performed biochemical, transcriptome, proteome, and biomarker analyses to characterize the cellular and molecular dysregulations of this non-human primate model. RESULTS: We observed early changes of AD-related pathological proteins (cerebrospinal fluid Aß42 and phosphorylated tau) in PSEN1 mutant (ie, PSEN1-ΔE9) monkeys. Blood transcriptome and proteome profiling revealed early changes in inflammatory and immune molecules in juvenile PSEN1-ΔE9 cynomolgus monkeys. DISCUSSION: PSEN1 mutant cynomolgus monkeys recapitulate AD-related pathological protein changes, and reveal early alterations in blood immune signaling. Thus, this model might mimic AD-associated pathogenesis and has potential utility for developing early diagnostic and therapeutic interventions. HIGHLIGHTS: A dual-guide CRISPR/Cas9 system successfully mimics AD PSEN1-ΔE9 mutation by genomic excision of exon 9. PSEN1 mutant cynomolgus monkey-derived fibroblasts exhibit disrupted PSEN1 endoproteolysis and increased Aß secretion. Blood transcriptome and proteome profiling implicate early inflammatory and immune molecular dysregulation in juvenile PSEN1 mutant cynomolgus monkeys. Cerebrospinal fluid from juvenile PSEN1 mutant monkeys recapitulates early changes of AD-related pathological proteins (increased Aß42 and phosphorylated tau).

Transcriptomic and proteomic investigations identify PI3K-akt pathway targets for hyperthyroidism management in rats via polar iridoids from radix Scrophularia.

High-polarity iridoids from Radix Scrophulariae (R. Scrophulariae) offer a range of benefits, including anti-inflammatory, antioxidant, antitumour, antibacterial, antiviral, and antiallergic effects. Although previous studies have indicated the potential of R. Scrophulariae for hyperthyroidism prevention and treatment, the specific active compounds involved and their mechanisms of action are not fully understood. This study explored the effects of high-polarity iridoid glycosides from R. Scrophulariae on hyperthyroidism induced in rats by levothyroxine sodium. The experimental design included a control group, a hyperthyroidism model group, and a group treated with iridoid glycosides. Serum triiodothyronine (T3) and thyroxine (T4) levels were quantified using an enzyme-linked immunosorbent assay (ELISA). Transcriptomic and proteomic analyses were applied to liver samples to identify differentially expressed genes and proteins. These analyses were complemented by trend analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The effectiveness of key factors was further examined through molecular biology techniques. ELISA results indicated a notable increase in T3 and T4 in the hyperthyroid rats, which was significantly mitigated by treatment with iridoid glycosides. Transcriptomic analysis revealed 6 upregulated and 6 downregulated genes in the model group, showing marked improvement following treatment. Proteomic analysis revealed changes in 30 upregulated and 50 downregulated proteins, with improvements observed upon treatment. The PI3K-Akt signalling pathway was investigated through KEGG enrichment analysis. Molecular biology methods verified the upregulation of Spp1, Thbs1, PI3K, and Akt in the model group, which was reversed in the treatment group. This study revealed that highly polar iridoids from R. Scrophulariae can modulate the Spp1 gene and Thbs1 protein via the PI3K-Akt signalling pathway, suggesting a therapeutic benefit for hyperthyroidism and providing a basis for drug development targeting this condition.

Inhibition of topoisomerase 2 catalytic activity impacts the integrity of heterochromatin and repetitive DNA and leads to interlinks between clustered repeats.

DNA replication and transcription generate DNA supercoiling, which can cause topological stress and intertwining of daughter chromatin fibers, posing challenges to the completion of DNA replication and chromosome segregation. Type II topoisomerases (Top2s) are enzymes that relieve DNA supercoiling and decatenate braided sister chromatids. How Top2 complexes deal with the topological challenges in different chromatin contexts, and whether all chromosomal contexts are subjected equally to torsional stress and require Top2 activity is unknown. Here we show that catalytic inhibition of the Top2 complex in interphase has a profound effect on the stability of heterochromatin and repetitive DNA elements. Mechanistically, we find that catalytically inactive Top2 is trapped around heterochromatin leading to DNA breaks and unresolved catenates, which necessitate the recruitment of the structure specific endonuclease, Ercc1-XPF, in an SLX4- and SUMO-dependent manner. Our data are consistent with a model in which Top2 complex resolves not only catenates between sister chromatids but also inter-chromosomal catenates between clustered repetitive elements.

Exploiting viral vectors to deliver genome editing reagents in plants.

Genome editing holds great promise for the molecular breeding of plants, yet its application is hindered by the shortage of simple and effective means of delivering genome editing reagents into plants. Conventional plant transformation-based methods for delivery of genome editing reagents into plants often involve prolonged tissue culture, a labor-intensive and technically challenging process for many elite crop cultivars. In this review, we describe various virus-based methods that have been employed to deliver genome editing reagents, including components of the CRISPR/Cas machinery and donor DNA for precision editing in plants. We update the progress in these methods with recent successful examples of genome editing achieved through virus-based delivery in different plant species, highlight the advantages and limitations of these delivery approaches, and discuss the remaining challenges.

Inhibition of JNK ameliorates rod photoreceptor degeneration in a mouse model of retinitis pigmentosa.

Retinitis pigmentosa (RP) is an inherited eye disease that causes progressive vision loss. Microglial activation and inflammation play essential roles in photoreceptor degeneration in RP, although the underlying mechanisms remain unclear. Here, we examined the progressive degeneration of photoreceptors in rd1 mice, a mouse model of RP. We investigated the molecular changes in various retinal cells in rd1 mice using single-cell RNA sequencing and found that potentiation of JNK signaling is associated with photoreceptor degeneration in RP. Moreover, inflammation-related molecules, which function downstream of JNK, are elevated in RP. Furthermore, inhibiting JNK alleviates microglial activation and rescues photoreceptor degeneration in rd1 mice. Thus, our findings suggest that targeting JNK is a promising approach for slowing RP progression.

The influence of ferroptosis on the in vitro OGD/R model in rat microglia.

OBJECTIVE: We aimed to explore the influence of ferroptosis on an oxygen-glucose deprivation/reoxygenation (OGD/R) model in primary rat microglia. METHODS: Primary microglia were extracted from rats and cultured in vitro. The cells were subjected to a hypoxic environment for 6 h in a glucose-free medium, and then re-oxygenated for 24 h in DMEM/F12. Rat microglia were pretreated with the ferroptosis activator erastin and the ferroptosis inhibitor ferrostatin 1 for 24 h, followed by detection of cell cycle progression and apoptosis by flow cytometry. Intracellular total iron levels were measured. In addition, the relative levels of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) were determined using enzyme-linked immunosorbent assay. The protein levels of 15-lox2, GPX4, SLC7A11, ACSL4, and TFR1 were examined by western blotting. RESULTS: Compared with rat microglia subjected to OGD/R, pretreatment with erastin did not influence cell apoptosis but significantly enhanced total iron levels, MDA, and ROS levels, whereas it reduced SOD levels. Moreover, it upregulated ACSL4, TFR1, and 15-lox2 and downregulated GPX4 and SLC7A11. Pretreatment with ferrostatin 1 significantly inhibited cell apoptosis and cell cycle arrest in the G0/G1 phase. It significantly reduced total iron levels, MDA, and ROS levels and enhanced SOD levels, which also downregulated ACSL4, TFR1, and 15-lox2, and upregulated GPX4 and SLC7A11. CONCLUSION: Our study showed that inhibition of ferroptosis is favorable against potential OGD/R-induced damage in rat microglia.

Genotype of pioneer plant Miscanthus is not a key factor in the structure of rhizosphere bacterial community in heavy metal polluted sites.

Miscanthus is a common pioneer plant with abundant genetic variation in abandoned mines in southern China. However, the extent to which genetic differentiation among species modulates rhizosphere bacterial communities remains unclear. Miscanthus samples were collected from 26 typical abandoned heavy-metal mines with different soil types in southern China, tested using 14 pairs of simple sequence repeats (SSR) primers, and classified into two genotypes based on Nei's genetic distance. The structure and diversity of rhizosphere bacterial communities were examined using 16 S rRNA sequencing. The results showed that among the factors affecting the rhizosphere bacterial community structure of Miscanthus samples, the role of genotype was not significant, and geographical conditions were the most important factors, followed by pH and total organic carbon (TOC). The process of rhizospheric community assembly varied among different genotypes; however, the recruited species and their abundances were similar. Collectively, we provided an approach based on genetic differentiation to quantify the relative contribution of genotypes to the rhizosphere bacterial community, demonstrating that genotypes contribute less than soil conditions. Our findings provide new insights into the role of host genetics in the ecological processes of plant rhizosphere bacterial communities in abandoned mines and provide theoretical support for microbe-assisted phytoremediation.

Hormone Regulation in Testicular Development and Function.

The testes serve as the primary source of androgens and the site of spermatogenesis, with their development and function governed by hormonal actions via endocrine and paracrine pathways. Male fertility hinges on the availability of testosterone, a cornerstone of spermatogenesis, while follicle-stimulating hormone (FSH) signaling is indispensable for the proliferation, differentiation, and proper functioning of Sertoli and germ cells. This review covers the research on how androgens, FSH, and other hormones support processes crucial for male fertility in the testis and reproductive tract. These hormones are regulated by the hypothalamic-pituitary-gonad (HPG) axis, which is either quiescent or activated at different stages of the life course, and the regulation of the axis is crucial for the development and normal function of the male reproductive system. Hormonal imbalances, whether due to genetic predispositions or environmental influences, leading to hypogonadism or hypergonadism, can precipitate reproductive disorders. Investigating the regulatory network and molecular mechanisms involved in testicular development and spermatogenesis is instrumental in developing new therapeutic methods, drugs, and male hormonal contraceptives.