Search Results (50)

Spigelian hernia (SH) is an infrequent aponeurotic defect in Spiegel’s semilunar line. The literature on pediatric SH is scarce. A comprehensive review of the previous literature was conducted. Eligible studies were identified by searching primary medical bibliography databases, and a pooled analysis of published case-level data was performed. Medians and interquartile ranges were used to describe the quantitative variables and proportions for categorical variables. The Kruskal–Wallis, Mann–Whitney U, and Fisher’s exact tests were used to compare group variables. Spearman’s and Pearson’s correlation analyses were used to assess the degree of correlation between variables, while Cramér’s V was applied to evaluate the degree of association among the variables. A p-value < 0.05 (two-tailed) was considered statistically significant. Our search identified 82 publications reporting on 123 patients (106 male, 86.2%), with an age range of 0–21 years. Forty-seven patients (38.2%) had a left-sided SH, fifty-six (45.5%) had a right-sided SH, and thirteen (10.6%) had a bilateral SH. Traumatic SH, mostly from bicycle injuries, accounted for 45 cases (36.6%), while 41 (33.3%) were associated with undescended testis (UDT). In this series of published cases, hernia incarceration/strangulation (I/S) was reported in 15 patients (12.2%), who were significantly younger (p = 0.02). Surgical correction was performed in 95 cases (77.2%), 14 of them laparoscopically, with a 35.7% conversion rate. Eight cases (6.5%) were managed conservatively. Overall, outcomes were favorable. SH is an infrequent pediatric condition that, based on the synthesized literature, predominantly affects males. The published cases suggest two main clinical phenotypes: a congenital form, often linked to ipsilateral UDT, and an acquired form, typically resulting from trauma. Analysis of the reported data indicates a higher risk of incarceration in early childhood. Surgical treatment is the most frequently reported approach with generally favorable outcomes, whereas the evidence for conservative management remains limited. This comprehensive review highlights the dual nature of pediatric SH and underscores the need for a high index of suspicion in relevant clinical scenarios. Full article

Male infertility, as a globally significant reproductive health issue, remains idiopathic in over 40% of cases. Reproductive disorders in males induced by environmental pollutants, such as di(2-ethylhexyl) phthalate (DEHP), have garnered considerable attention in recent years. DEHP induces testicular oxidative stress and ferroptosis via its active metabolite MEHP, thereby leading to spermatogenic dysfunction. Lycium barbarum polysaccharide (LBP), a traditional food and medicine homologous substance, exhibits potential antioxidant and reproductive protective properties. However, the underlying mechanism by which LBP intervenes in the toxicity induced by DEHP remains to be elucidated. This study explored the protective effect and molecular mechanism of LBP on DEHP-induced testicular injury through in vivo and in vitro experiments. The result showed that DEHP exposure (150 mg/L in free drinking water for 6 weeks) significantly decreased testicular weight, sperm concentration, and sperm motility in mice, while DEHP exposure induced pathological damage to testicular tissue, as evidenced by cavitation of seminiferous tubules, reduced numbers of spermatocytes, and vacuolar degeneration of Sertoli cells. However, LBP (450 mg/L) treatment significantly reversed testicular damage and sperm parameters. In vitro, MEHP reduced the viability of GC2 cells (spermatocyte cell line) and TM4 cells (Sertoli cell line), and LBP significantly restored cell activity. Mechanistically, exposure to DEHP/MEHP results in iron overload (elevated levels of free Fe²⁺), lipid peroxidation (increased MDA and reduced GSH), and dysregulated expression of key proteins involved in ferroptosis and iron homeostasis within the testis and cells. Furthermore, it was demonstrated that when NRF2 was specifically inhibited by ML385 or silenced via siRNA, the protective effects of LBP were abrogated, thereby validating the critical role of NRF2 in the regulation of iron homeostasis by LBP. In conclusion, LBP mitigates DEHP-induced testicular injury by activating NRF2 to regulate iron homeostasis in Sertoli cells and spermatocytes cells. This study not only offers a potential strategy for the prevention and treatment of male reproductive disorders caused by DEHP exposure, but also underscores the reproductive protective effects and application prospects of LBP in this context. Full article

Male infertility is a pathological condition that affects many subjects and for which a progressive increase in cases has been observed in recent years. The mechanisms underlying male reproductive system dysfunction are not fully understood and the specific drugs use has not produced optimal results. Therefore, the focus on developing new therapeutic options to prevent or treat this dysfunction is continuously growing. Defective sperm function has been associated with oxidative stress (OS) due to reactive oxygen species (ROS) excessive production. OS is related to mitochondrial dysfunction, lipid peroxidation, DNA damage and fragmentation, and ultimately sperm cell death. Many defense mechanisms to protect from ROS injuries have been developed; natural antioxidants, such as vitamin C and E are able to interact with oxidizing radicals, neutralizing them. Interestingly, resveratrol (RSV), a natural polyphenol with proven health-promoting actions, has been found to be an effective free radical scavenger in several in vitro and in vivo models, providing protection against OS. In this review, we discussed mechanisms related to the modulation of redox homeostasis in the testis and how the alteration of these processes can determine a damage in testicular function; particularly, we focused on the antioxidant properties of RSV that could give beneficial effects in preserving male fertility. Full article

Tramadol, a central analgesic drug, is used to treat moderate to severe pain but can cause reproductive disorders. The pathogenesis of tramadol-induced reproductive damage may involve increased oxidative stress, pro-inflammatory cytokines, ATP depletion, and reduced antioxidant levels. In this study, subjects were divided into four groups: healthy control (HC), tramadol only (TM), ATP only (ATP), and ATP + tramadol (ATM). ATP was administered intraperitoneally at 4 mg/kg, and tramadol was administered orally at 50 mg/kg. Distilled water was given to the HC group. This regimen was repeated for three weeks. At the end of the treatment, testicular tissues from six rats in each group were analyzed biochemically and histopathologically after euthanasia. The remaining rats’ reproductive functions were evaluated. Long-term tramadol exposure resulted in oxidative stress, inflammation in testicular tissue, and reduced male reproductive capacity. Thinning of seminiferous tubule walls and thickening of basement membrane, irregularity in germ cells, increase in interstitial connective tissue, congestion in vessels, increase in Leyding cells and hyperplasia were found in the TM group. ATP treatment significantly reduced tramadol-induced increases in oxidants and pro-inflammatory cytokines, reversed the decline in antioxidants, and mitigated infertility in testicular tissue. Furthermore, ATP preserved the morphology of the testicular tissue. These findings suggest that ATP may offer therapeutic potential for tramadol-induced infertility. Full article

Testicular torsion is a common emergency in adolescents, and can lead to severe ischemia reperfusion injury (IRI). LncRNA H19 has been shown to increase during ischemia, but its role in testicular IRI remains unknown. Focusing on this research gap, we utilized H19 biallelic mutant mice and Sertoli cell line (TM4) to construct in vivo and in vitro models of ischemia/reperfusion (I/R) and oxygen–glucose deprivation/reperfusion (OGD/R). Compared to WT I/R mice, H19^−/− I/R mice showed milder tissue disorganization and cell loss, with a more intact blood–testis barrier (BTB). The cell viability decreased, ROS levels and apoptosis-related factors such as Bax/Bcl-2 increased in TM4 cells after OGD/R, whereas these changes were reversed when H19 was knocked down followed by OGD/R (si-H19+OGD/R). In contrast, over-expression of H19 in TM4 cells exacerbates OGD/R-induced cell apoptosis. Through in-depth analysis of KEGG-enriched pathways, the PI3K/AKT pathway was identified as a potential target of H19 modulation. Western blotting confirmed that, in OGD/R cells, elevated H19 levels were accompanied by the excessive AKT phosphorylation and the tight junction marker ZO-1 degradation; and in si-H19+OGD/R cells, the decreased AKT phosphorylation was recovered and the up-regulated ZO-1 expression was weakened simultaneously via using the AKT activator SC79. These results suggest that inhibiting H19 in OGD/R cells might preserve the integrity of the BTB by reversing the excessive phosphorylation of AKT. Moreover, H19 deficiency in si-H19+OGD/R cells alleviated the disturbances in glycolysis, fatty acid biosynthesis, and amino acid metabolism. Our study indicates that H19 might be a potential therapeutic target for clinic testicular I/R treatment. Full article

Inflammation and increased oxidative stress in testicular tissue are documented side effects of torsion of the testicles. The preventive role of Bromelain (Bro) against testicle torsion-induced ischemia/reperfusion (I/R) injury was investigated in this research. Five groups of six animals each were created: ischemia, Ischemia+Reperfusion (I+R), Ischemia+Reperfusion+Bromelain (I+R+Bro; 10 mg/kg), control (sham), and Bromelain (Bro; 10 mg/kg). An I/R damage resulted from two hours of 720° clockwise twisting of the left testis. Blood samples and epididymal sperm were collected after reperfusion to analyze sperm parameters (recovery, motility, viability, and morphology) and cytokines that promote inflammation (IL-1β, IL-6, and TNF-α). Using Western blotting, testicular tissue was examined for histopathological alterations, antioxidant enzymes (GSH, SOD), lipid peroxidation (MDA), apoptosis, and survival-related proteins (TLR4, Caspase-3, Bcl-2, NRF-2, HO-1, PI3K, mTOR, AKT-1). While raising the activities of GSH and SOD, two antioxidant enzymes, Bro administration dramatically reduced MDA concentrations. The I+R+Bro group had significantly reduced amounts of cytokines that promoted inflammation compared to the I+R group. Bro’s protective properties are also attributed to proteins that are altered by it and participate in the apoptosis and survival of cells. Sperm morphology, motility, and concentration notably improved in the bromelain-treated group, according to spermatological examination. Testicular samples treated with bromelain showed less tissue damage according to histological evaluations than the untreated I+R group. These findings imply that Bro has anti-inflammatory, anti-apoptotic, and antioxidant qualities. It effectively reduces oxidative stress and inflammation by modulating the PI3K/Akt/mTOR and NRF-2/HO-1 pathways, hence minimizing I/R injury. Full article

Objectives: The present study describes the comparative effect of 24-week supplementation of beeswax alcohol (BWA, Raydel^®, 0.5% and 1.0%, wt/wt) and coenzyme Q₁₀ (CoQ₁₀, 0.5% and 1.0%, wt/wt) on plasma oxidative variables and the prevention of organ injury in adult zebrafish subjected to a high-cholesterol (HC, 4%, wt/wt) and -D-galactose (Gal, 30%, wt/wt) diet. Methods: Adult zebrafish were fed various HC+Gal diets enriched with either BWA or CoQ₁₀. After 24 weeks of dietary intervention, blood and organs were harvested for subsequent biochemical and histological evaluations. Results: The HC+Gal-elevated plasma oxidative variables were reverted by the consumption of BWA, marked by the lowest plasma malondialdehyde (MDA) level and highest sulfhydryl content. The HC+Gal-impaired zebrafish swimming ability (staggering movement) was substantially recovered by BWA, manifested by a ~three-fold (p < 0.001) enhancement in swimming distance and speed. Also, the intake of BWA affected the morphology of HC+Gal-compromised kidney and induced histological changes by mitigating reactive oxygen species (ROS) production and cellular senescence, which was markedly more effective than the results seen in the CoQ₁₀ group. Likewise, BWA proved effective in preventing HC+Gal-induced testis damage, apparent in the 48.3% (p < 0.05) higher spermatozoa and 26.3% (p < 0.01) reduced interstitial space between the seminiferous tubules. BWA substantially prevented HC+Gal-induced ovary damage by suppressing oxidative stress, lipid deposition and senescence, leading to the restoration of mature vitellogenic oocyte counts. Conclusion: BWA demonstrated a greater ability than CoQ₁₀ to enhance plasma antioxidant status, suppress ROS generation, delay organ aging and alleviate HC+Gal-induced adversity in zebrafish. Full article

Oxidative stress triggered by testicular torsion and detorsion in young males could negatively impact future fertility. Using a rat animal model for testicular IRI (tIRI), we aim to study the induction of autophagy (ATG) during testicular ischemia and tIRI and the role of oxidative-stress-induced c-Jun N-terminal Kinase (JNK) as a cytoprotective mechanism. Sixty male Sprague-Dawley rats were divided into five groups: sham, ischemia only, ischemia+SP600125 (a JNK inhibitor), tIRI only, and tIRI+SP600125. The tIRI rats underwent an ischemic injury for 1 h followed by 4 h of reperfusion, while ischemic rats were subjected to 1 h of ischemia only without reperfusion. Testicular-ischemia-induced Beclin 1 and LC3B expression was associated with decreased p62/SQSTM1 expression, increased ATP and alkaline phosphatase (AP) activity, and slightly impaired spermatogenesis. SP600125 treatment improved p62 expression and reduced the levels of Beclin 1 and LC3B but did not affect ATP or AP levels. The tIRI-induced apoptosis lowered the expression of the three ATG proteins and AP activity, activated caspase 3, and caused spermatogenic arrest. SP600125-inhibited JNK during tIRI restored sham levels to all investigated parameters. This study emphasizes the regulatory role of JNK in balancing autophagy and apoptosis during testicular oxidative injuries. 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

Chemotherapy is an important factor leading to male infertility. It is crucial to discover safe and effective treatments to prevent male reproductive injury caused by chemotherapy. The Ganoderma lucidum polysaccharide peptide (GLPP) has multiple pharmacological activities. The purpose of this study was to determine whether GLPP could protect the male sperm production from chemotherapeutic injury using a mouse model, with testicular damage induced by cyclophosphamide (CP). CP (50 mg/kg/day) was injected intraperitoneally into male ICR mice gavaged with different doses of GLPP at certain spermatogenic stages. The experimental results showed that GLPP alleviated the CP-induced reduction in reproductive organ coefficients and sperm parameters and reduced the morphological damage of testicular tissues in a dose-dependent manner. GLPP significantly improved the reproductive index, sperm-related parameters, sex hormone levels, and histological testis architecture at different spermatogenic stages. Furthermore, GLPP significantly increased superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), Nrf2, and HO-1, and decreased malondialdehyde (MDA) and Keap-1 in the testicular tissue, indicating reduced oxidative stress. In addition, GLPP limited CP-induced apoptosis via a reduction in Bax expression and increase in Bcl-2 expression. This study suggests that GLPP plays a protective role in spermatogenesis by reducing chemotherapeutic injury and might be developed into drug for male patients receiving chemotherapy. Full article

Busulfan, an indispensable medicine in cancer treatment, can cause serious reproductive system damage to males as a side effect of its otherwise excellent therapeutic results. Its widespread use has also caused its accumulation in the environment and subsequent ecotoxicology effects. As a Chinese medicine, Wulingzhi (WLZ) has the effects of promoting blood circulation and improving female reproductive function. However, the potential effects of WLZ in male reproduction and in counteracting busulfan-induced testis damage, as well as its probable mechanisms, are still ambiguous. In this study, busulfan was introduced in a mouse model to evaluate its production of the testicular damage. The components of different WLZ extracts were compared using an untargeted metabolome to select extracts with greater efficacy, which were further confirmed in vivo. Here, we demonstrate abnormal spermatogenesis and low sperm quality in busulfan-injured testes. The WLZ extracts showed a strong potential to rehabilitate the male reproductive system; this effect was more prominent in room-temperature extracts. Additionally, both water and ethanol WLZ extracts at room temperature alleviated various busulfan-induced adverse effects. In particular, WLZ recovered spermatogenesis, re-activated arginine biosynthesis, and alleviated the increased oxidative stress and inflammation in the testis, ultimately reversing the busulfan-induced testicular injury. Collectively, these results suggest a promising approach to protecting the male reproductive system from busulfan-induced adverse side effects, as well as those of other similar anti-cancer drugs. Full article

Acute kidney injury (AKI) is a public health burden with increasing morbidity and mortality rates and health care costs. Acute tubular necrosis (ATN) is the most common cause of AKI. Cisplatin (CIS) is a platinum-based chemotherapeutic agent used in the treatment of a wide variety of malignancies such as lung, breast, ovary, testis, bladder, cervix, and head and neck cancers. Autophagy plays an important role in AKI. Galectin-3 (Gal-3) is significantly increased in renal tubules in AKI; however, its role in autophagy is not well understood. Male C57B6/J and B6.Cg-Lgals3 <^{tm 1 Poi}>/J Gal-3 knockout (KO) mice were used to induce AKI using a CIS mouse model of ATN. Renal Gal-3 and autophagy proteins’ expression were measured using standard histologic, immunofluorescent, and enzyme-linked immunosorbent assay techniques. The data were presented as the mean ± S.E. Statistically significant differences (p < 0.05) were calculated between experimental groups and corresponding control groups by one-way analysis of variance. There was a significant increase in renal concentrations of Gal-3 in the Gal-3 wild-type CIS-treated mice when compared with sham control mice. There were significantly higher concentrations of renal LC3B, ATG13, Ulk-1, Beclin, ATG5, ATG12, ATG9A, and p-AMPK in the CIS-treated Gal-3 KO mice than in the Gal-3 wild-type CIS-treated mice. Further, there were significantly higher concentrations of mTOR, p- NF-κB, beta-catenin, and p62 in the kidneys of the Gal-3 wild-type CIS-treated mice than in the Gal-3 KO CIS-treated mice. Our findings affirm the connection between Gal-3 and autophagy, revealing its central role as a connector with prosurvival signaling proteins. Gal-3 plays a pivotal role in orchestrating cellular responses by interacting with prosurvival signal pathways and engaging with autophagy proteins. Notably, our observations highlight that the absence of Gal-3 can enhance autophagy in CIS-induced ATN. Full article

Endothelial injury, inflammatory infiltrate and fibrosis are the predominant lesions in the testis of bulls with besnoitiosis that may result in sterility. Moreover, fibroblasts, which are key players in fibrosis, are parasite target cells in a Besnoitia besnoiti chronic infection. This study aimed to decipher the molecular basis that underlies a drift toward fibrosis during the disease progression. Transcriptomic analysis was developed at two times post-infection (p.i.), representative of invasion (12 h p.i.) and intracellular proliferation (32 h p.i.), in primary bovine aorta fibroblasts infected with B. besnoiti tachyzoites. Once the enriched host pathways were identified, we studied the expression of selected differentially expressed genes (DEGs) in the scrotal skin of sterile infected bulls. Functional enrichment analyses of DEGs revealed shared hallmarks of cancer and early fibrosis. Biomarkers of inflammation, angiogenesis, cancer, and MAPK signaling stood out at 12 h p.i. At 32 h p.i., again MAPK and cancer pathways were enriched together with the PI3K–AKT pathway related to cell proliferation. Some DEGs were also regulated in the skin samples of naturally infected bulls (PLAUR, TGFβ1, FOSB). We have identified potential biomarkers and host pathways regulated during fibrosis that may hold prognostic significance and could emerge as potential therapeutic targets. Full article

Diabetic testicular damage is quite a common and significant complication in diabetic men, which could result in infertility. The natural fertility rate of type 1 diabetes men is only 50% because of testicular damage. This research first aimed to explore the intervention effect of C3G on testicular tissue damage induced by diabetes. Here, a streptozotocin-induced type 1 diabetic rat model was established, and then C3G was administered. After 8 weeks of C3G supplementation, the symptoms of diabetes (e.g., high blood glucose, lower body weight, polydipsia, polyphagia) were relieved, and at the same time that sperm motility and viability increased, sperm abnormality decreased in C3G-treated diabetic rats. Furthermore, the pathological structure of testis was restored; the fibrosis of the testicular interstitial tissue was inhibited; and the LH, FSH, and testosterone levels were all increased in the C3G-treated groups. Testicular oxidative stress was relieved; serum and testicular inflammatory cytokines levels were significantly decreased in C3G-treated groups; levels of Bax, Caspase-3, TGF-β1 and Smad2/3 protein in testis decreased; and the level of Bcl-2 was up-regulated in the C3G-treated groups. A possible mechanism might be that C3G improved antioxidant capacity, relieved oxidative stress, increased anti-inflammatory cytokine expression, and inhibited the apoptosis of spermatogenic cells and testicular fibrosis, thus promoting the production of testosterone and repair of testicular function. In conclusion, this study is the first to reveal that testicular damage could be mitigated by C3G in type 1 diabetic rats. Our results provide a theoretical basis for the application of C3G in male reproductive injury caused by diabetes. Full article

Di-(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer, which can cause damage to male reproductive organs, especially the atrophy of the testis. Meanwhile, DEHP can also lead to a decrease in testicular zinc content, but the role of zinc remains unclear. This study aims to prepare oyster peptide-zinc complex (OPZC) to alleviate DEHP-induced reproductive damage in mice. OPZC was successfully obtained through electron microscopy, X-ray diffraction, and thermogravimetric analysis, with stable structure and high water-solubility. Low dose oyster peptide-zinc complex (OPZCL) significantly reduced the reproductive damage caused by DEHP in mice. Further research had shown that OPZCL restored the content of serum hormones and the activity of oxidative stress kinases to normal, while also normalizing testicular zinc and selenium levels. In addition, it also recovered the disorder of gut microbiota, reduced the proportion of Bacteroides, increased the abundance of Ligilactobacillus, and restored the proportion of Acidobacteriota, Chloroflexi, and Proteobacteria. Therefore, OPZCL can relieve the reproductive damage caused by DEHP in mice by restoring testicular zinc homeostasis and the composition of intestinal microbiota, indicating that OPZCL has a potential protective effect on male reproductive health. Full article