Search Results (391)

The grey squirrel, an invasive species, threatens the Eurasian red squirrel’s conservation, particularly in Umbria, Italy. Understanding its reproductive biology is essential to limiting its reproductive success. This study investigates the NGF system and its receptors (NTRK1 and p75NTR) in the testes of male grey squirrels, following prior research on female reproductive biology. NGF plays a role in testicular morphogenesis and spermiogenesis in animals and humans. As part of the LIFE Project U-SAVEREDS, eighteen squirrels were captured and classified into three morphotypes (immature, pubertal, and active spermatogenesis). NGF and its receptors were analyzed using real-time PCR, western blotting, immunohistochemistry, and plasma levels measured via ELISA. NGF qPCR expression levels were significantly higher during puberty compared to the immature and spermatogenesis stages (p < 0.01). Immunohistochemistry revealed NGF in Leydig cells, with stronger staining in pubertal and mature squirrels, while NTRK1 was found in Leydig cells in immature squirrels and germ cells in pubertal and mature ones. NGF receptors were observed in Sertoli cells in pubertal and mature squirrels. Plasma NGF levels showed a significant upregulation in pubertal squirrels (135.80 ± 12 pg/mL) compared to those in the immature (25.60 ± 9.32 pg/mL) and spermatogenesis stages (34.20 ± 6.06 pg/mL), with a p value < 0.01. The co-localization of NGF and its receptors suggests that NGF, produced by Leydig cells, regulates testis development and reproductive success through autocrine or paracrine mechanisms, potentially involving an unidentified pathway. Full article

Purpose: Over the past 40–50 years, demographic shifts and the obesity epidemic have coincided with significant changes in lifestyle habits, including a rise in excessive alcohol consumption. This increase in alcohol intake is a major public health concern due to its far-reaching effects on human health, particularly on metabolic processes and male reproductive function. This narrative review focuses on the role of alcohol consumption in altering metabolism and impairing testicular function, emphasizing the potential damage associated with both acute and chronic alcohol intake. Conclusion: Chronic alcohol consumption has been shown to disrupt liver function, impair lipid metabolism, and dysregulate blood glucose levels, contributing to the development of obesity, metabolic syndrome, and related systemic diseases. In terms of male reproductive health, alcohol can significantly affect testicular function by lowering testosterone levels, reducing sperm quality, and impairing overall fertility. The extent of these effects varies, depending on the frequency, duration, and intensity of alcohol use, with chronic and abusive consumption posing greater risks. The complexity of alcohol’s impact is further compounded by individual variability and the interaction with other lifestyle factors such as diet, stress, and physical activity. Despite growing concern, research on alcohol’s effects remains inconclusive, with significant discrepancies across studies regarding the definition and reporting of alcohol consumption. These inconsistencies highlight the need for more rigorous, methodologically sound research to better understand how alcohol consumption influences metabolic and reproductive health. Ultimately, a clearer understanding is essential for developing targeted public health interventions, particularly in light of rising alcohol use, demographic changes, and the ongoing obesity crisis. Full article

Introduction: Currently, progesterone is notably absent from conventional feminizing hormone therapies for transgender women. Anecdotal reports indicate the potential for health advantages following the incorporation of progesterone into treatment regimens. The primarily female hormone, progesterone naturally surges in women during the menstrual luteal phase. When administered exogenously, it may expedite bodily changes that are pivotal for gender transition. Progesterone holds promise as a potential remedy for various health conditions prevalent in the transgender woman population. Methods: This narrative review synthesizes existing literature and presents a comprehensive account of the administration of exogenous progesterone in transgender women. A literature search was conducted using the PubMed, Embase, ScienceDirect, and ResearchGate databases. The following keywords were used in the search: progesterone, transgender, breast neoplasms, lactation, prostate, testicular neoplasms, and thrombosis. These terms were combined using Boolean operators. The results of the initial search were screened by three independent reviewers based on their relevance to the topic under study. Results: A total of 104 studies were initially identified as meeting the criteria for inclusion. Following an assessment based on the contents of the title, abstract, and full text, 39 studies were deemed eligible for inclusion. A critical examination of health outcomes was conducted across key sections, including breast development, mental health, lactation, cancer risk (breast and prostate), thrombosis, and nervous and other systems. Discussion: The use of progesterone in the transgender woman population is a topic that has yet to be sufficiently researched. The limited sample size, short follow-up periods, and lack of randomization restrict the potential for achieving a robust scientific evidence base. In order to gain a fuller understanding of this topic, findings from studies on contraception, hormone replacement therapy, and animal models were considered. Conclusions: Progesterone may have a beneficial effect on the bodies of transgender women without significant adverse health effects. Further investigation through well-designed studies is recommended. Randomized controlled trials that include various dosages, broad and long-term effects, and precise demographics are needed. There is an immediate need for more knowledge to create appropriate patent and clinical practice guidelines. Full article

The correlation between epigenetic alterations and the pathophysiology of human infertility is progressively being elucidated with the discovery of an increasing number of target genes that exhibit altered expression patterns linked to reproductive abnormalities. Several genes and molecules are emerging as important for the future management of human infertility. In men, microRNAs (miRNAs) like miR-34c, miR-34b, and miR-122 regulate apoptosis, sperm production, and germ cell survival, while other factors, such as miR-449 and sirtuin 1 (SIRT1), influence testicular health, oxidative stress, and mitochondrial function. In women, miR-100-5p, miR-483-5p, and miR-486-5p are linked to ovarian reserve, PCOS, and conditions like endometriosis. Mechanisms such as DNA methylation, histone modification, chromatin restructuring, and the influence of these non-coding RNA (ncRNA) molecules have been identified as potential perturbators of normal spermatogenesis and oogenesis processes. In fact, alteration of these key regulators of epigenetic processes can lead to reproductive disorders such as defective spermatogenesis, failure of oocyte maturation and embryonic development alteration. One of the primary factors contributing to changes in the key epigenetic regulators appear to be oxidative stress, which arises from environmental exposure to toxic substances or unhealthy lifestyle choices. This evidence-based study, retracing the major epigenetic processes, aims to identify and discuss the main epigenetic biomarkers of male and female fertility associated with an oxidative imbalance, providing future perspectives in the diagnosis and management of infertile couples. Full article

The genetic landscape of urologic cancers has evolved with the identification of actionable mutations that impact diagnosis, prognosis, and therapeutic strategies. This narrative review consolidates existing literature on genetic mutations across key urologic cancers, including bladder, renal, prostate, upper tract urothelial, testicular, and penile. The review highlights mutations in DNA damage repair genes, such as BRCA1/2 and PTEN, as well as pathway alterations like FGFR and PD-L1 overexpression. These mutations influence tumor behavior and therapeutic outcomes, emphasizing the need for precision oncology approaches. Molecular profiling, through tools like next-generation sequencing, has revolutionized patient care by enabling targeted treatment strategies, especially in cancers with distinct molecular subtypes such as luminal or basal bladder cancer and clear cell renal carcinoma. Emerging therapies, including FGFR inhibitors and immune checkpoint blockade, offer new treatment avenues, although resistance mechanisms remain a challenge. We also emphasize the importance of biomarker identification for personalized management, especially in metastatic settings where treatment intensification is often required. Future research is needed to further elucidate our understanding of the genetics affecting urologic cancers, which will help develop novel, individualized therapies to enhance oncologic outcomes. Full article

PTD-FNK, a synthetic anti-apoptotic protein, has been shown to potently alleviate cellular injuries. However, the effects of PTD-FNK on oxidative defense in boar testicular Sertoli cells (SCs) against oxidative injury has not been explored. In this study, we show that exposure of SCs to 100 mg/L lipopolysaccharide (LPS) for 12 h leads to decreased survival rate, superoxide dismutase (SOD) activity, and increased malondialdehyde (MDA). Treatment with 0.01 nmol/L PTD-FNK for 4 h significantly enhanced the activity of SOD, catalase (CAT), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) in SCs. Concurrently, PTD-FNK treatment effectively reduced the production of reactive oxygen species (ROS) and the levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG) in SCs. Moreover, using His pull-down and LC-MS techniques, we identified PTD-FNK-interacting proteins and confirmed that this protective effect may be mediated by the regulation of the Keap1-Nrf2 signaling pathway by PTD-FNK. Therefore, PTD-FNK alleviates LPS-induced oxidative stress via the Keap1/Nrf2 pathway, providing novel insights for the development of therapeutic agents targeting testicular oxidative damage. Full article

2-Bromopalmitate (2-BP) is a palmitoylation inhibitor that can prevent the binding of palmitic acid to proteins, thereby exhibiting significant effects in promoting inflammation and regulating the immune system. However, limited research has been conducted regarding the direct effects of 2-BP on the animal organism. Therefore, we probed mice injected with 2-BP for altered expression of inflammatory genes, with a focus on demonstrating changes in the intestinal flora as well as damage to the reproductive system. Our findings indicate that 2-BP can induce substantial inflammatory responses in visceral organs and cause testicular dysfunction. The key changes in the gut microbiota were characterized by an abundance of Firmicutes, Clostridiales, Rikenellaceae_RC9_gut_group, Desulfovibrio, Muribaculaceae, and Alistipes, and their metabolism has been intricately linked to visceral inflammation. Overall, the findings of this study provide a sound scientific basis for understanding the impact of high doses of 2-BP in mammals, while also offering crucial support for the development of preclinical models to suppress palmitoylation. Full article

Exposure to pesticides such as paraquat and 2,4-dichlorophenoxyacetic acid (2,4-D) has been linked to harmful health effects, including alterations in male reproduction. Both herbicides are widely used in developing countries and have been associated with reproductive alterations, such as disruption of spermatogenesis and steroidogenesis. The thyroid axis and Ca²⁺-permeable ion channels play a key role in these processes, and their disruption can lead to reproductive issues and even infertility. This study evaluated the short-term effects of exposure to commercial herbicides based on paraquat and 2,4-D on gene expression in rat testes. At the molecular level, exposure to paraquat increased the expression of the thyroid hormone transporters monocarboxylate transporter 8 (Mct8) and organic anion-transporting polypeptide 1C1 (Oatp1c1) and the thyroid receptor alpha (TRα), suggesting a possible endocrine disruption. However, it did not alter the expression of the sperm-associated cation channels (CatSper1-2) or vanilloid receptor-related osmotically activated channel (Trpv4) related to sperm motility. In contrast, exposure to 2,4-D reduced the expression of the Mct10 transporter, Dio2 deiodinase, and CatSper1, which could affect both the availability of T3 in testicular cells and sperm quality, consistent with previous studies. However, 2,4-D did not affect the expression of CatSper2 or Trpv4. Deregulation of gene expression could explain the alterations in male reproductive processes reported by exposure to paraquat and 2,4-D. These thyroid hormone-related genes can serve as molecular biomarkers to assess endocrine disruption due to exposure to these herbicides, aiding in evaluating the health risks of pesticides. Full article

Background: Hemoglobin, Albumin, Lymphocyte, and Platelet Score (HALP) is an accessible score that is easily reproducible from routine laboratory testing while also reflecting patients’ immune-nutritional status. Along with other immuno-nutritional scores, such as the Prognostic Nutrition Index (PNI), HALP has been associated with a number of clinical and pathological features. The goal of our study was to evaluate the prognostic utility of HALP and PNI scores in testicular germ cell cancer (GCT) patients. Methods: This case-only study included 203 testicular GCT patients who were classified according to the disease stage and HALP and PNI cut-offs. Complete blood count and albumin concentration were routinely determined. Results: The values of HALP and PNI significantly differed among different clinical stages (p < 0.05). Moreover, they clearly exposed a significantly higher risk of advanced clinical stage development for those testicular GCT patients with lower values of HALP and PNI (p < 0.05). Finally, lower score levels were associated with larger tumor size (p < 0.05). Conclusion: Our investigation could provide evidence that specific immune-nutritional scores can help distinguish individuals diagnosed with testicular GCT who are more likely to be identified with advanced disease stages. Full article

Numerous genes govern male reproduction, modulating testicular development and spermatogenesis. Our study leveraged RNA-Seq to explore candidate genes and pivotal pathways influencing fecundity in an F1 hybrid of Southdown × Hu sheep testes across four developmental milestones: M0 (0 months old, newborn), M3 (3 months old, sexually immature), M6 (6 months old, sexually mature), and Y1 (1 years old, adult). Histological examination using hematoxylins and eosin staining revealed that the cross-sectional area of the spermatid tubules and the number of supportive cells increased in the other groups, as compared to the M0 group. The cross-sectional area of the vasculature and the number of supporting cells were found to be significantly increased in all other groups in comparison to the M0 group. We conducted GO and KEGG analyses of the differentially expressed genes (DEGs) in the three comparison groups and identified key pathways, including cAMP, MAPK, ECM–receptor interactions, PI3K-Akt, and FOXO signaling, which are closely related to testicular development and spermatogenesis. Notably, alternative splicing (AS) events were markedly elevated in M6 and Y1 stages. Key genes like GATA4, GATA6, SMAD4, SOX9, YAP1, ITGB1 and MAPK1 emerged as significantly enriched in these pathways, potentially orchestrating the transition from immature to mature testes in sheep. These findings offer valuable insights into male reproductive potential and can inform strategies for optimizing animal breeding. Full article

Blood–testis barrier (BTB) genes are crucial for the cellular mechanisms of spermatogenesis as they protect against detrimental cytotoxic agents, chemicals, and pathogens, thereby maintaining a sterile environment necessary for sperm development. BTB proteins predominantly consist of extensive tight and gap junctions formed between Sertoli cells. These junctions form a crucial immunological barrier restricting the intercellular movement of substances and molecules within the adluminal compartment. Epithelial tight junctions are complex membrane structures composed of various integral membrane proteins, including claudins, zonula occludens-1, and occludin. Inter-testicular cell junction proteins undergo a constant process of degradation and renewal. In addition, the downregulation of genes crucial to the development and preservation of cell junctions could disrupt the functionality of the BTB, potentially leading to male infertility. Oxidative stress and inflammation may contribute to disrupted spermatogenesis, resulting in male infertility. L-cysteine is a precursor to glutathione, a crucial antioxidant that helps mitigate damage and inflammation resulting from oxidative stress. Preclinical research indicates that L-cysteine may offer protective benefits against testicular injury and promote the expression of BTB genes. This review emphasizes various BTB genes essential for preserving its structural integrity and facilitating spermatogenesis and male fertility. Furthermore, it consolidates various research findings suggesting that L-cysteine may promote the expression of BTB-associated genes, thereby aiding in the maintenance of testicular functions. Full article

Many anuran survival strategies involve hydric regulation, and reproduction is not different. The aquaporin (AQP) family plays an important role in water transport and regulation in many tissues, including the male gonad. The testes undergo various stages of change during the reproductive cycle, and water balance is an important factor for ensuring reproductive success. Considering the relevance of water control in testicular development in anurans and the lack of research regarding the tissue localization of AQP in the male gonad, the present study investigated the expression of three AQPs (1, 2, and 9) in the testis of the neotropical anuran species Leptodactylus podicipinus during two different periods of the reproductive cycle (reproductive and non-reproductive). AQP1 and 2 immunoreactions were found in early germ cells, spermatozoa, Leydig cells, and Sertoli cells, which were more frequently expressed within the reproductive period. AQP1 was also found in the testicular blood vessels. AQP9 was identified predominantly in the epithelium of the intratesticular ducts of reproductive-period individuals. This study presents, for the first time, the localization of AQP1, AQP2, and AQP9 in the testes of an anuran species and the differences in their location during two distinct periods of the reproductive cycle. Full article

Seasonal reproduction is a mammalian behavior that has developed over an extended evolutionary period and requires animals to respond to external environmental changes to facilitate reproduction. In this study, we investigated the role of PIWI-interacting RNA (piRNA) in the seasonal reproduction of plateau zokors (Eospalax baileyi). piRNA expression profiles in plateau zokor testes during both breeding and non-breeding seasons were examined. The piRNAs had a distinctive ping-pong signature and ranged from 27 to 32 nt with a peak at 30 nt. Testicular piRNAs predominantly aligned to specific genomic regions, including repeat and gene regions. Analysis of the piRNA–mRNA interaction network and functional enrichment of differentially expressed piRNAs targeting mRNAs revealed their association with testicular development and spermatogenesis. Significantly, PIWIL4 is an mRNA gene that interacts with piRNA and exhibits high expression levels within the testes during the non-breeding phase. This study provides a foundation to improve our understanding of piRNA regulatory mechanisms during testicular development and spermatogenesis in seasonally reproducing animals and, specifically, in the plateau zokor. Full article

Iron is a key element in spermatogenesis; its metabolic pathway in the testis is strictly regulated. Alterations in iron metabolism are linked to various diseases, including cancer, and changes in iron metabolism-related proteins have been observed in multiple human, mouse and canine tumors. There is limited knowledge about iron metabolism in canine non-neoplastic and neoplastic testes. This study aimed to explore the immunohistochemical expression of molecules involved in iron uptake and storage [Transferrin Receptor 1 (TfR1), ferritin (FTH1), nuclear receptor coactivator 4 (NCOA4)] and PCNA in canine non-neoplastic and neoplastic testicular samples. Non-neoplastic testes showed moderate TfR1 expression in developing germ cells and Sertoli cells, high NCOA4 cytoplasmic immunostaining in the Sertoli cells and occasional cytoplasmic immunopositivity for FTH1 in the spermatogonia and Sertoli cells. In contrast, Leydig cell tumors (LCTs) and Diffuse Type Seminoma (DSEM) exhibited increased expression of TfR1, along with higher PCNA expression, suggesting a higher iron need for proliferation. Intratubular Type Seminoma (ITSEM) showed a higher FTH1 expression, indicating greater iron storage, while the increased NCOA4 expression in the LCTs and DSEM suggested ferritinophagy to release iron for proliferation. Sertoli cell tumors (SCTs) showed only NCOA4 expression. These preliminary findings highlight potential molecular targets for developing new anti-neoplastic treatments in canine testicular tumors. Full article

The expression pattern of GLOD4 in the testis and its regulatory effect on testicular cells was explored in goats to enhance our understanding of spermatogenesis and improve reproduction in breeding rams. In this study, we demonstrated the localization of GLOD4 in testicular cells using immunohistochemistry and subcellular localization analyses. Subsequently, we analyzed the GLOD4 expression pattern in four age-based groups (0, 6, 12, and 18 months old) using real-time quantitative polymerase chain reaction (qRT-PCR) and protein blotting. Finally, we performed GLOD4 silencing and overexpression studies in Leydig cells (LCs) and explored the effects on cell proliferation, the cell cycle, steroid hormone secretion and the expression of candidate testosterone hormone-regulated genes. GLOD4 was mainly expressed in Leydig cells, and the subcellular localization results showed that the GLOD4 protein was mainly localized in the cytoplasm and nucleus. Silencing of GLOD4 significantly suppressed the mRNA expression levels of the testosterone secretion-related genes CYP11A1, 3β-HSD, and CYP17A1 and the mRNA expression levels of cell cycle-related genes CDK6, PCNA, and Cyclin E. Moreover, the cell cycle was blocked at the G2/M phase after GLOD4 silencing, which significantly suppressed testosterone secretion. In contrast, GLOD4 overexpression significantly increased the mRNA expression levels of the testosterone secretion-related genes CYP11A1, 3β-HSD, and CYP17A1 and increased the expression of the cell cycle-related genes CDK6, PCNA, and Cyclin E. Moreover, GLOD4 overexpression promoted the cell cycle from G0/G1 phases to enter the S phase and G2/M phases, promoted the secretion of testosterone. Taken together, our experimental results indicate that GLOD4 may affect the development of cells in Qianbei Ma goats of different ages by influencing the cell cycle, cell proliferation, and testosterone hormone synthesis. These findings enhance our understanding of the functions of GLOD4 in goats. Full article