Search Results (485)

Infertility is a growing global health concern, with male infertility contributing to nearly half of all cases. While conventional semen analysis often overlooks functional impairments, oxidative stress has emerged as a key factor affecting sperm quality. Notably, oxidative stress is elevated in obesity, a rising epidemic affecting more than 1 in 8 people worldwide. This study examines the role of deoxycholic acid (DCA), a secondary bile acid that is elevated in obesity, and its potential to induce oxidative stress and impair sperm function. Semen samples from healthy donors were incubated with DCA, and its effects on sperm motility, viability, capacitation, and oxidative stress markers were assessed. Sperm motility and viability were evaluated using computer-assisted semen analysis (CASA) and hypo-osmotic swelling (HOS) tests, while sperm capacitation was measured via tyrosine phosphorylation (P-Tyr) and acrosome reaction (AR). Oxidative stress markers were quantified using flow cytometry. While progressive motility and viability remained unchanged, DCA reduced hyperactive motility, P-Tyr, and acrosome reaction and increased oxidative stress markers in spermatozoa. These findings suggest that secondary bile acids can disrupt sperm function through oxidative mechanisms, affecting non-conventional semen parameters that may go undetected in standard analyses. This underscores the gut-testis axis’s role in male infertility and highlights the need for more comprehensive diagnostics and targeted therapies. Full article

Background: Spermatogenesis depends on precise cytoskeletal regulation, particularly the microtubule system; however, the mechanisms governing tubulin homeostasis during meiosis are poorly defined. While the E3 ubiquitin ligase Hyd (Hyperplastic discs), the Drosophila homolog of UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5), plays roles in diverse cellular processes, its precise role in male meiosis is unknown. This study aims to define the function and expression dynamics of Hyd during Drosophila spermatogenesis and elucidate whether it acts independently of its canonical ligase activity. Methods: Using Drosophila genetics, immunofluorescence, CRISPR/Cas9-mediated tagging, and mosaic clonal analysis, we characterized Hyd expression and function in the testis. Hyd knockdown and rescue experiments were performed with wild-type and catalytically inactive transgenes. β2-tubulin expression and microtubule organization were assessed in hyd mutant clones. Results: Hyd exhibits a dynamic, stage-specific expression pattern, localizing to nuclear and meiotic structures. Hyd loss led to meiotic arrest, disrupted spindle formation, aberrant centrosome behavior, and failure of spermatid elongation. Genetic rescue demonstrated that both wild-type and catalytically inactive Hyd partially restored spermatid elongation, indicating a catalysis-independent role. Furthermore, Hyd deficiency resulted in β2-tubulin overexpression, disrupted microtubule organization, and abnormal spermatocyte morphology. Conclusions: Hyd ensures meiotic fidelity in Drosophila by fine-tuning β2-tubulin expression independently of its E3 ubiquitin ligase activity. These findings reveal a non-proteolytic function for UBR5/Hyd in cytoskeletal regulation during male gametogenesis, providing new insights into tubulin homeostasis in meiosis. Full article

Testicular stiffness is a potential indicator of spermatogenic activity. Herein, we investigated the relationship between testicular stiffness and intratesticular morphology in Syrian hamsters by using a robotic system with a micro-force sensor. Animals were divided into control, sham-operated, and surgically induced cryptorchidism groups. Testicular stiffness, testis weight and size, and Johnsen score data for sham and crypt groups were partially derived from our previous study and reanalysed. Testicular stiffness and histological parameters were analysed, including tunica albuginea thickness, seminiferous tubule occupancy, tubule diameter, intratubular cell-layer thickness, peritubular lamina propria thickness, and Leydig cell numbers. Compared with those of sham and normal controls, cryptorchid testes showed significantly lower stiffness and marked morphological changes, such as reduced tubule occupancy and diameter, thinner intratubular cell layers, thickened tunica albuginea and peritubular lamina propria, and increased numbers of Leydig cells. Decreased testicular stiffness and the Johnsen score, a standard index of spermatogenic function, were strongly related to these structural changes. These findings indicate that structural changes in the testes caused by impaired spermatogenesis are related to measurable differences in tissue stiffness. This study supports using mechanical properties as non-invasive quantitative indices to evaluate testicular function in animal models, offering a novel approach for future research in experimental andrology. Full article

Background: Classical swine fever virus (CSFV) is a highly contagious and fatal disease in pigs and wild boars. While hunting and bait vaccination are effective for CSFV eradication, additional strategies are needed to control wild boar populations. This study aimed to develop an oral vaccine, Flc-LOM-GnRHx3, by inserting gonadotropin-releasing hormone (GnRH) epitopes into the Flc-LOM clone. Methods: The Flc-LOM-GnRHx3 strain was rescued from CPK cells and propagated to high titers in MDBK cells. Male boars (20 weeks old) received three doses (10^5.0 TCID₅₀/ml/dose) of Flc-LOM-GnRHx3 either orally or intramuscularly at 2-week intervals. Anti-CSFV E2 antibodies were detected via immunofluorescence and Western blotting. Results: Both vaccination routes induced anti-GnRH antibodies and reduced testosterone levels. Testis size and weight were slightly lower than controls, with seminiferous tubule and spermatid deformities observed in 52.5% of intramuscularly vaccinated pigs and 20.8% of orally vaccinated pigs. Conclusions: Flc-LOM-GnRHx3 demonstrates potential as a dual-function oral vaccine that can eradicate CSFV and impair reproductive capacity in wild boars, offering a novel approach for integrated disease control and population management. Full article

The Nile tilapia (Oreochromis niloticus), a key aquaculture species, displays marked sexual growth dimorphism, with males growing faster than females. This process is governed by intricate interactions between antagonistic regulators, including transcription factors, growth factors, and steroid hormones, operating through sex-specific developmental pathways. While circular RNAs (circRNAs) are known to modulate gene expression by sponging microRNAs (miRNAs), their role in teleost sex differentiation remains poorly understood. To address this gap, we profiled circRNA expression in tilapia gonads by constructing six circRNA libraries from testes and ovaries of 180 days after hatching (dah) fish, followed by high-throughput sequencing. We identified 6564 gonadal circRNAs distributed across all 22 linkage groups, including 226 differentially expressed circRNAs (DECs; 108 testis-biased, 118 ovary-biased). Functional enrichment analysis linked their host genes to critical pathways such as cAMP signaling, cell adhesion molecules, and—notably—sexual differentiation processes (e.g., estrogen signaling, oocyte meiosis, and steroid hormone biosynthesis). Furthermore, we deciphered competing endogenous RNA (ceRNA) networks, uncovering circRNA–miRNA–mRNA interactions targeting germ cell determinants, sex-specific transcription factors, and steroidogenic enzymes. This study provides the first systematic exploration of circRNA involvement in tilapia sex differentiation and gonadal differentiation, offering novel insights into the post-transcriptional regulation of sexual dimorphism. Our findings advance the understanding of circRNA biology in fish and establish a framework for future studies on aquaculture species with similar reproductive strategies. Full article

Sugarcane wax-derived policosanol (POL) is well recognized for its multifaceted biological activities, particularly in dyslipidemia management, whereas sugar cane extract powder (SEP), prepared from whole sugar juice blended with supplementary components, has not been thoroughly investigated for its biological activities and potential toxicities. Herein, the comparative dietary effect of four distinct SEPs (SEP-1 to SEP-4) and Cuban sugarcane wax extracted POL were examined to prevent the pathological events in high-cholesterol diet (HCD)-induced hyperlipidemic zebrafish. Among the SEPs, a 14-week intake of SEP-2 emerged with the least zebrafish survival probability (0.75, log-rank: χ² = 14.1, p = 0.015), while the POL supplemented group showed the utmost survival probability. A significant change in body weight and morphometric parameters was observed in the SEP-2 supplemented group compared to the HCD group, while non-significant changes had appeared in POL, SEP-1, SEP-3, and SEP-4 supplemented groups. The HCD elevated total cholesterol (TC) and triglyceride (TG) levels were significantly minimized by the supplementation of POL, SEP-1, and SEP-2. However, an augmented HDL-C level was only noticed in POL-supplemented zebrafish. Likewise, only the POL-supplemented group showed a reduction in blood glucose, malondialdehyde (MDA), AST, and ALT levels, and an elevation in sulfhydryl content, paraoxonase (PON), and ferric ion reduction (FRA) activity. Also, plasma from the POL-supplemented group showed the highest antioxidant activity and protected zebrafish embryos from carboxymethyllysine (CML)-induced toxicity and developmental deformities. POL effectively mitigated HCD-triggered hepatic neutrophil infiltration, steatosis, and the production of interleukin (IL)-6 and inhibited cellular senescence in the kidney and minimized the ROS generation and apoptosis in the brain. Additionally, POL substantially elevated spermatozoa count in the testis and safeguarded ovaries from HCD-generated ROS and senescence. The SEP products (SEP-1, SEP-3, and SEP-4) showed almost non-significant protective effect; however, SEP-2 exhibited an additive effect on the adversity posed by HCD in various organs and biochemical parameters. The multivariate examination, employing principal component analysis (PCA) and hierarchical cluster analysis (HCA), demonstrates the positive impact of POL on the HCD-induced pathological events in zebrafish, which are notably diverse, with the effect mediated by SEPs. The comparative study concludes that POL has a functional superiority over SEPs in mitigating adverse events in hyperlipidemic zebrafish. Full article

Spermatogenesis in teleosts is essential for reproductive function; however, it varies considerably among species. The testis of the viviparous molly fish (Poecilia sphenops) was examined using both ultrastructural and immunohistochemical methods. The testis displays a restricted lobular type, where germ cells develop synchronously within Sertoli cell-forming cysts. Transmission electron microscopy (TEM) revealed all stages of spermatogenesis. Mature sperm are at the apex of the cysts and migrate toward the sperm ducts. Sperm duct epithelium is lined by cuboidal cells joined by tight junctions, with apical cilia and desmosomal complexes contributing to transport and structural integrity. The sperm ducts showed strong Periodic Acid–Schiff (PAS)-positive expression among negative stained spermatocysts. Centrally, a cavity serves as a storage area for spermatozoa that are organized into unencapsulated bundles known as spermatozeugmata. Sertoli cells exhibited extended cytoplasmic processes that supported developing germ cells, whereas Leydig cells occupied the interstitial tissue, contributing to hormonal regulation. Immunohistochemical labeling demonstrated strong vimentin expression in Sertoli cells and telocytes, indicating their mesenchymal origin and structural role. Calretinin expression was confined to Leydig cells and certain ductal epithelial cells, supporting its use as a marker for steroidogenic and secretory functions. These findings provide new insights into the testicular specialization of P. sphenops, highlighting key somatic–germ cell interactions, ductal adaptations, and marker expression patterns that underlie male reproductive success in viviparous fish. Full article

Fibrous sheath interacting proteins 1 and 2 (FSIP1 and FSIP2) are evolutionarily conserved testis-specific antigens, exclusively expressed in germ cells of adult human tissues, where they play essential roles in spermatogenesis and testicular development. Aberrant re-expression of FSIP1 and FSIP2, however, has been frequently reported in multiple malignancies, driving oncogenic processes including uncontrolled proliferation, invasion, migration, and metastasis, and correlating with unfavorable clinical outcomes. Their restricted expression in normal tissues, together with their consistent association with poor prognosis across cancer types, highlights their potential as diagnostic biomarkers, therapeutic targets, and prognostic indicators. This review summarizes the structural features and biological functions of the FSIP family, emphasizes recent advances in elucidating their regulatory roles in tumor-associated signaling pathways, and outlines the major challenges and future perspectives in this emerging field. Full article

In Nile tilapia, one of the most important aquaculture species, males are larger than females, and an all-male monosex culture offers significant economic benefits. Although the pituitaries of genetic female (XX) and genetic male (XY) tilapia have identical expression levels of follicle-stimulating hormone (fsh), FSH receptor (fshr) expression remains relatively low in XY-undifferentiated gonads and then increases following morphological sex differentiation. The expression patterns of genes related to androgen biosynthesis in XY-undifferentiated gonads are similar to those of fshr during testis differentiation. This might imply that FSH has a potential function in testis differentiation through regulating the expression of genes related to androgen biosynthesis. To determine whether FSH signaling regulated androgen biosynthesis, we microinjected recombinant FSH (rFsh) into XY larvae during the early sex-differentiation stage. We compared the expression of various genes related to testis differentiation after injection. The genes hsd3b, cyp17a1, dmrt1, and gsdf were found to have higher expression in the rFsh treatment group. These results suggest that FSH signaling can activate androgen biosynthesis by regulating steroidogenic enzymes, including hsd3b and cyp17a1. Moreover, injected rFsh can upregulate dmrt1, which has a positive effect on the expression of gsdf. Therefore, during testis differentiation and development, FSH plays a role in both androgen synthesis and the expression of genes related to testis differentiation in Nile tilapia. Full article

Background: Manganese (Mn) is a trace element essential for multiple physiological and biological processes. The testis plays a key role in male reproduction by producing sperm and synthesizing male hormones. This study investigates how Mn deficiency affects testicular development, spermatogenesis, and the blood–testis barrier (BTB), and evaluates associated variations in oxidative stress to explore potential mechanisms. Methods: A Mn-deficient diet was used to induce Mn deficiency in mice, with MnCl₂ administered via intraperitoneal injection. Mn levels in testicular tissue were measured by atomic absorption spectrometry. Testis and sperm morphology were assessed by H.E. and sperm staining. BTB markers were analyzed using immunofluorescence, Western blot, and qPCR. Oxidative stress was evaluated biochemically. Nrf2 pathway changes were detected by qPCR and Western blot. Results: The results indicated that Mn deficiency dramatically decreased the testicular index, caused abnormal testicular tissue structure, and significantly decreased Johnsen’s score. At the same time, sperm density and motility were significantly reduced, and the sperm deformity rate was significantly increased. In addition, the BTB function was impaired, as indicated by the significantly down-regulated expression of tight junction proteins including Occludin, ZO-1, JAM-A, and Claudin-11. As the oxidative stress levels increased, the mRNA and protein expression levels of molecules (including Nrf2 and HO-1) related to the Nrf2 signaling pathway were significantly down-regulated, while its inhibitor Keap1 exhibited significantly up-regulated expression. Notably, after supplementing MnCl₂, all the above abnormal indicators were significantly improved. Conclusions: Mn deficiency can lead to testicular tissue damage, decreased sperm quality, and BTB dysfunction, and the potential mechanism is probably closely associated with the increase in the oxidative stress level mediated by the Nrf2 pathway. Full article

Gene duplications are considered to be the major evolutionary resource of novel functions. The gene family Esf2/ABP1 is conserved in metazoan organisms from yeast to humans. Here we performed a search and characterization of Esf2/ABP1 homologs in the Drosophila genus. Whereas in the majority of Drosophila species this gene family is represented by only a single gene, in the melanogaster and suzukii subgroups recurrent gene duplications arose, providing 47 homologous genes located on the X chromosome. To study the evolutionary history of duplicates, we performed phylogenetic, functional domain, and tissue-specific expression analyses. We revealed a male-specific and testis-biased transcription pattern of duplicated copies in Drosophila melanogaster and Drosophila sechellia compared to ubiquitous expression of the parental gene. The amplification of 21 repeated paralogs within the heterochromatic piRNA cluster resulted in the ovarian-specific transformation of these repeats into piRNAs in D. melanogaster. In three species of the suzukii subgroup, Esf2/ABP1 genes evolved with domain diversification: in addition to RNA-binding ABT1-like domain preservation, all homologous proteins acquired expanded intrinsically disordered regions. By studying the duplicated copies of the Esf2/ABP1 family in Drosophila, we offer insight into how novel gene functions emerge and are maintained, contributing to life’s diversity and complexity. Full article

Male infertility is a growing global concern with increasing prevalence in both developing and developed nations. While many associations between environmental factors and male infertility have been explored, the relationship between sleep deprivation and male infertility remains underexplored. This narrative review examines the reported effects of sleep deprivation on the Hypothalamic––Gonadal (HPG) axis, Hypothalamic–Pituitary–Adrenal (HPA) axis, oxidative stress, and testicular function, and their consequential effects on male infertility. Disruption of the HPG axis results in altered follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, leading to fluctuation in testosterone levels, negatively affecting spermatogenesis and other critical reproductive processes. Activation of the HPA axis, often due to stress, elevates cortisol levels, which, in turn, suppresses gonadotropin-releasing hormone (GnRH), impairing reproductive function. Reactive oxidative species (ROS) accumulate in periods of oxidative stress and have been shown to damage sperm and reduce their quality. The blood–testis barrier (BTB) is disrupted in states of sleep deprivation, leading to decreased sperm quality. A literature review was conducted using PubMed and Google Scholar to assess peer-reviewed studies from 1990 to 2024, revealing a complex interplay between sleep deprivation and male reproductive dysfunction. While existing studies support a link between sleep disturbances and hormonal dysregulation, further research is needed to establish causal relationships and identify potential therapeutic interventions. Addressing sleep deprivation may represent a modifiable factor in improving male fertility outcomes. Full article

In this study, oyster fermentation broth (OFB) was prepared by fermenting oysters with yeast, and its effects on oxidative stress and reproductive damage induced by tripterygium glycosides (TG) in male rats were investigated. Component analysis revealed that OFB contained bioactive substances including proteins (1.19 g/L), taurine (0.76 g/L), organic acids (2.30 mg/mL), polyphenols (123.00 mg GAE/L), flavonoids (1.97 mg RE/L), and zinc (1.10 mg/L). In vitro study revealed that OFB exhibited notable antioxidant activity, with a total antioxidant capacity of 1.28 U/mL, and DPPH, ABTS, and hydroxyl radical scavenging rates of 55.80%, 69.54%, and 48.36%, respectively. Animal experiments showed that, compared with the TG-induced model group, rats administered both low-dose (5 mL/kg) and high-dose (10 mL/kg) OFB showed significantly increased testis and seminal vesicle + prostate indices, sperm count, and serum testosterone (T) levels and decreased sperm malformation rate (p < 0.01 for all). Histological analysis of the testis revealed an increased number of spermatogenic cells and sperm within the seminiferous tubules, along with ameliorated pathological conditions compared to the model group. Potential mechanisms might be related to OFB increasing the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) enzymes and reducing levels of malondialdehyde (MDA) in testis (p < 0.01). The findings demonstrated that OFB successfully alleviated TG-induced reproductive damage in male rats, which might be attributed to its excellent antioxidant effect. The study offers valuable insights for producing functional foods from oysters and further validates OFB’s efficacy in promoting reproductive function. Full article

Sexual behavior is a complex process in which the brain plays an active role. In the male rat, stimuli from the female are perceived through sensory receptors related to olfaction, hearing, vision, and the perigenital area, priming the individual for a sexual response. This process culminates with ejaculation and the deposition of semen into the uterine tract with the aim of achieving fertilization. The brain plays a fundamental role in both generating motivation and executing male sexual behavior. Meanwhile, the spinal cord, through the autonomic nervous system and the pelvic ganglion, transmits information to the reproductive organs, including the testes. Currently, there is extensive evidence demonstrating the involvement of various brain structures in the regulation of sexual behavior, as well as specific regions of the spinal cord involved in the control of ejaculation. For instance, the medial preoptic area (MPOA) has been shown to regulate the secretion of pituitary hormones, which in turn modulate the function of reproductive organs. Among these, testosterone production is particularly notable, as this hormone not only directly affects reproductive organs but also exerts a modulatory role on brain nuclei responsible for sexual behavior. Although there is a reciprocal regulation between the nervous and endocrine systems, it is important to note that the execution of sexual behavior also impacts peripheral structures, such as the major pelvic ganglion (MPG) and the testis, preparing the organism for reproduction. The purpose of this mini-review is to provide an overview of the main brain nuclei involved in the regulation of sexual behavior, as well as the spinal cord regions implicated in reproduction. Finally, we discuss how these structures may alter their function in the context of neurodegenerative diseases, aiming to introduce readers to this field of study. Full article

Background and Objectives: Currently, infertility is one of the major problems affecting up to 12% of couples worldwide, with more than a quarter of cases being male-related. It is assumed that Leukocyte-poor platelet-rich plasma (LP-PRP) can improve the function of germ cells and serve as a regenerative substrate as a source of biologically active substances that play an important role in the process of spermatogenesis in infertile men. We aimed to evaluate the proliferation, apoptosis, and growth factors of germ cells after the administration of LP-PRP in patients with non-obstructive azoospermia. Materials and Methods: The study used archival material (paraffin blocks of testicular biopsies) of patients with non-obstructive azoospermia aged 21–34 years (n = 41; associated diagnosis: varicocele). We confirm that no interventions or biopsies were performed as part of the study itself. They were injected bilaterally into the spermatic cord and in the region of the lower pole of the testis under ultrasound control were injected with PRP once a week for 6 weeks. Biopsies were immunohistochemical reactions with antibodies to Ki-67, Bcl-2, caspase 3 and p53, IGF-1, TGF-β, and VEGF-A. Results: Immunohistochemical study of testicular biopsies after LP-PRP injection revealed an increase in the number of cells stained for proliferation proteins (Ki-67) and anti-apoptosis (Bcl-2), IGF-1, TGF-β, VEGF-A; decrease caspase-3- and p53-positive cells. Conclusions: In LP-PRP, platelet α-granule growth factors, which are key regulators of the cell cycle of germ cells, demonstrate restoration of the proliferative-apoptotic balance, confirmed by the expression levels of Ki-67, Bcl-2, caspase 3, and p53 in patients with non-obstructive azoospermia. In human testicular biopsies, the administration of LP-PRP led to an exponential release of numerous growth factors from platelet α-granules, which, based on their regenerative properties, improved the morphological and immunohistochemical picture of the germinal epithelium in non-obstructive azoospermia. Full article