Organic compounds present in environmental pollution are currently regarded as major health threats. Phenanthrene (Phe), a polycyclic aromatic hydrocarbon, impairs testicular function through oxidative stress, leading to the failure of spermatogenesis. This study aimed to explore the potential beneficial effects of photobiomodulation (PBM) on testicular tissue and sperm parameters following Phe exposure in mice. Twenty-four adult male mice, aged 8 weeks, were randomly divided into three groups: control, Phe, and Phe+PBM. In the Phe and Phe+PBM groups, mice received Phe (500 ng/kg) via gavage every 48 hours for 5 weeks. Following Phe exposure, the testes of the Phe+PBM mice were irradiated with laser photons every other day for 35 days. After euthanasia, epididymal tails and testes were collected for molecular and histological analyses. PBM significantly improved sperm count, motility, and viability (p<0.0001). Moreover, reactive oxygen species production, lipid peroxidation, and apoptosis were markedly reduced in the testicular tissue of the laser-treated mice (p<0.0001). Improvements were also observed in seminiferous epithelium thickness and cell distribution following PBM (p<0.0001). Laser therapy significantly mitigates testicular damage from Phe exposure by reducing oxidative stress and apoptosis biomarkers, thereby improving testicular tissue and sperm parameters.

Chlorpyrifos (CPF) and bifenthrin (BF) are two of the most commonly used pesticides in the agriculture sector, which may accumulate in the environment and cause biotoxicity. The current study was conducted to check the potential toxicity of CPF and BF on Hypophthalmichthys molitrix. The 96 h-LC50 of CPF, BF, and their mixture were calculated as 11.2 μg/L, 4.7 μg/L, and 0.8 μg/L, respectively. A total of 120 adult fish distributed into 12 aquariums (n = 10 fish/aquarium) weighing 118 ± 5 were used; sublethal concentrations of CPF (3.72 μg/L), BF (1.34 μg/L), and CPF + BF mixture (0.26 μg/L) were administered for 30 days during the experiment. Results showed a decline in antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) in the liver, kidney, and testis of fish in all exposure groups. Whereas the levels of reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) were increased. Similarly, insecticide exposure caused DNA damage in terms of increased tail length, scattered chromatin with reduced %DNA in the head. Histoarchitectural variations showed more prominent damage in BF and CPF + BF-treated groups. Liver histopathology showed necrosis, macrophage aggregation, and damaged hepatocytes, while in the kidney, tissue hemorrhage and fragmentation of convoluted tubules were evident in treated groups. Additionally, gonadal histopathology showed dilated seminiferous tubules, wider lumen with reduced sperm count in treated groups. Results of the present study suggest that CPF and BF have the potential to cause hepatic, renal, and testicular toxicity in H. molitrix with synergism.

Unraveling the reproductive toxicity mechanisms of emerging environmental contaminants 6:2 and 8:2 diPAPs in male mice: an integrated transcriptome-metabolome investigation.

The present study aimed to investigate the effects of taxifolin on cisplatin-induced testicular toxicity in rats. Twenty eight male Wistar Albino rats, 2 months old, weighing 250-300 g, were used in the study. The rats were randomly selected and four groups were created: sham (S) group, cisplatin (C) group, taxifolin (T) group and cisplatin+taxifoline (CT) group, with 7 rats in each group. On the first day of the study, a single intraperitoneal injection of 7 mg/kg cisplatin was administered to groups C and CT. Taxifolin (50 mg/kg) was given by oral gavage to T and CT groups for 7 days. On the eighth day of the study, all rats were sacrificed and testicular tissues were removed for analysis. Cisplatin caused significant histopathological changes in the testicular tissue, such as advanced deterioration of the seminiferous tubules, degeneration and desquamation in the seminiferous tubule epithelium, coagulation necrosis, and bleeding and edema in the intertubular area, as well as an increase in Cosentino scores and a decrease in Johnson scores. Cisplatin administration reduced membrane integrity, decreased sperm motility and density, and increased the rate of abnormal spermatozoon and dead spermatozoon. In the combined application of cisplatin and taxifoline, taxifoline significantly reduced the histopathological changes caused by cisplatin and rearranged the Cosentino and Johnson scores. It also increased membrane integrity and sperm motility and reduced the rate of abnormal spermatozoon. This study showed that cisplatin caused toxicity in testicular tissue and taxifolin could prevent cisplatin-induced testicular toxicity.

Diabetes mellitus, a chronic metabolic disorder marked by persistent hyperglycemia, often requires multifaceted therapeutic approaches. Although Arthrospira platensis exhibits antihyperglycemic properties, its bioactive compounds have limited bioavailability. This study synthesized selenium-functionalized A. platensis nanoparticles (Se-APNPs) using Na₂SeO₃ and evaluated their effects in diabetic mice. Arthrospira platensis powdered (raw material) (AP-P), Se-APNPs (10% and 20% v/v), infused AP-P (10% v/v), and glibenclamide were tested following diabetes induction via alloxan. The 10% Se-APNPs significantly lowered fasting glucose (84 mg/dL), outperforming glibenclamide, while infused AP-P showed superior wound healing (94.5%), comparable to the drug (96.6%). Growth performance was optimal in the 10% Se-APNP group, but higher concentrations indicated potential testicular toxicity. These findings highlight Se-APNPs as a promising approach for glycemic regulation and metabolic improvement, with infused AP-P excelling in wound repair. Dose optimization is crucial for maximizing efficacy and minimizing toxicity.

Metronidazole (MTZ), a widely used antiamoebic and antibacterial drug, has been linked to male reproductive damage. The aim of this study was to investigate Olea europaea L. and Equisetum arvense L. ethanol extracts for the protection against testicular toxicity and male infertility caused by MTZ, and to characterize the underlying mechanisms. Forty-two male rats were divided into six groups. The animals in group 1 served as the controls and received a daily oral dose (1 mL) of the vehicle. The animals in group 2 received metronidazole at doses of 400 mg/kg. Group 3 was treated with E. arvense extract at doses of 100 mg/kg. Group 4 was treated with O. europaea leaf extract at doses of 400 mg/kg. Group 5 was treated with metronidazole and E. arvense extract at doses of 400 and 100 mg/kg, respectively. Group 6 was treated with metronidazole with O. europaea leaf extract at doses of 400 and 400 mg/kg, respectively. The rats were given a daily oral dose of different treatments for 60 days, after which the animals were euthanized to study the histopathological and molecular changes in the testis and the sperm count in the epididymis. The testosterone levels, MDA levels, and GSH contents were also assessed in the rats in all groups. The findings revealed that the MTZ treatment caused a substantial increase in MDA levels and upregulated the NBN gene expression relative to the control. Moreover, the MTZ treatment produced significant reductions in the sperm count and viability, testosterone levels, and GSH content, and downregulated the INSL-3, STAR, HSD-3β, and CYP11A1 gene expression compared to the control. The adverse effects in testicular tissue were significantly reduced in rats given the O. europaea leaves and E. arvense treatment. The findings may show that MTZ can enhance testicular toxicity and infertility, but both plant extracts can prevent these harmful consequences.

Ethylene glycol monomethyl ether (EGME) is a testicular germ cell toxicant that selectively targets spermatocytes. In rats, male-only EGME exposure reduces mating success and can lead to an increase in resorbed fetuses. In a previous study, five-day exposure to 50, 60, or 75 mg/kg/d EGME in male rats led to a decrease in sperm motility and increase in retained spermatid heads with a LOAEL of 75 mg/kg/d. At 60 mg/kg/d, EGME exposure altered the proportion of sperm small RNA reads mapped to different small RNA categories and the distribution of read lengths. Because there is evidence that small non-coding RNAs (sncRNAs) in sperm regulate embryonic development, we analyzed sperm sncRNA data from EGME-treated male rats to identify differential expression at the individual RNA level. EGME treatment resulted in dose-dependent increases in the expression levels of microRNAs (miRNAs), piRNAs, and tRNA-derived small RNAs (tsRNAs). We identified 12 miRNAs that were differentially expressed at all EGME doses, with a monotonic, dose-dependent increase. High-confidence targets of these 12 miRNAs are known to be expressed in pre-implantation embryos and statistically enriched for Gene Ontology (GO) biological processes related to early development, such as cell fate commitment and regulation of developmental growth. These results demonstrated that the EGME-induced changes in sperm sncRNA levels were reproducible, dose-dependent, and provided a putative mechanism of paternal EGME effects on embryonic development, which will be investigated in future studies.

Cisplatin (Cis) has been widely used for treating many types of solid tumors. Despite its clinical effectiveness, Cis has a considerable risk of gonadal damage that may cause infertility. Morin hydrate (MH), a natural bioflavonoid, has been known for its antioxidant and anti-inflammatory effects. Our study aimed to investigate whether pretreatment with MH could protect against Cis-induced testicular toxicity. Thirty-five adult male rats were split into five groups (n = 7, each); control group received oral 0.5% CMC for 10days, MH group received oral MH (100mg/kg) for 10days, Cis group was given a single dose of Cis (7mg/kg, i.p) on day 5, (MH 50 + Cis) and (MH 100 + Cis) groups were pretreated with MH (50mg/kg) and (100mg/kg), respectively for 5days before Cis administration, and then, treatment was continued, with either doses, for further 5days. At the end of the study, blood and testicular tissues were collected for biochemical and histopathological studies. MH administration mitigated the testicular histopathological changes induced by Cis, increased sperm count and motility, and abrogated the abnormalities in sperm morphology. Further, MH enhanced antioxidant status and suppressed the inflammation via downregulating NF-κB and NLRP3 and inflammatory cytokines expression. Our in vitro study revealed that MH enhanced Cis-induced cytotoxicity against cancer cells, including PC3, MCF7, and HepG2. These findings suggested that MH could be applied in Cis chemotherapy regimens as a possible adjuvant therapy to enhance its effect and prevent Cis-induced testicular damage.

Lead acetate exposure induces male reproductive toxicity through oxidative stress and inflammation, impairing spermatogenesis and testosterone production. Umbelliferone (UMB), a coumarin derivative with antioxidant and anti-inflammatory properties, may counteract these adverse effects. This study evaluated the protective effects of UMB on lead acetate-induced testicular toxicity in male Wistar rats, with a focus on sperm parameters, antioxidant status, inflammatory markers, and testicular histology. Thirty-two male Wistar rats were assigned to four groups (n=8 each): control (saline), lead (50 mg/kg lead acetate [intraperitoneal], lead+UMB (25 mg/kg), and lead+UMB (50 mg/kg). Treatments were administered daily for 21 days. Sperm parameters (count, motility, viability, morphology) were assessed, alongside measurements of antioxidant enzyme levels (superoxide dismutase, catalase, glutathione), malondialdehyde (MDA), serum testosterone, and mRNA expression of tumor necrosis factor-α, interleukin-6 (IL-6), transforming growth factor-β, IL-10, Bcl-2-associated X protein (Bax), and B-cell lymphoma-2 (Bcl-2). Testicular histology was evaluated using hematoxylin and eosin staining. Lead exposure significantly reduced sperm quality, antioxidant enzyme levels, testosterone, and Bcl-2 expression, while increasing MDA, pro-inflammatory cytokines, and Bax expression (p<0.05). UMB (25 and 50 mg/kg) markedly improved sperm parameters, restored antioxidant levels, reduced MDA and inflammatory markers, increased testosterone and Bcl-2, and decreased Bax expression (p<0.01). Histological analysis demonstrated that UMB preserved testicular architecture. No significant differences were observed between the two UMB doses (p>0.05). UMB effectively mitigates lead-induced testicular toxicity by reducing oxidative stress, inflammation, and apoptosis, while improving sperm quality and testosterone levels. These findings suggest its potential as a therapeutic agent.

This study evaluates the safety, tolerability, pharmacokinetics, and tissue distribution of paclitaxel injection concentrate for nanodispersion (PICN), either as standalone treatment or in comparison with Abraxane® (AbX) and Oncotaxel (OtX, generic formulation of Taxol® from Sun Pharma). In vitro cytotoxicity was assessed in-HT-29, PC-3, SKOV3 and NCI H522 human cancer cell lines. Single- and multiple-dose toxicity studies were conducted in rodents evaluating clinical signs, hematology, histopathology, and organ-specific toxicity. Pharmacokinetic studies were performed in rats analyzing Paclitaxel (PtX) concentrations by LC-MS/MS. PICN demonstrated comparable in vitro cytotoxicity to OtX. Single- and repeat-dose toxicity studies revealed that PICN has similar toxicity profile with AbX, including reversible lymphoid depletion and irreversible testicular toxicity at higher doses. Known PtX class effects, myelosuppression and neuropathy was observed in both PICN and reference groups; with less pronounced effects in females. PICN (at 10 mg/kg) produced a lower reduction in pain threshold (~ 22%) compared to OtX (~ 43%), suggesting a reduced potential for neurotoxicity. PICN showed no local irritation following IV administration and no hemolytic potential in-vitro. It exhibited dose-proportional increases in Cmax and AUC0-inf across 5-20 mg/kg, with pharmacokinetic parameters comparable to AbX. Red blood cell (RBC) partitioning studies indicated balanced distribution for PICN compared to OtX, and slightly lower RBC exposure than AbX. PICN also demonstrated moderate PtX distributions with concentrations higher than AbX but substantially lower than OtX in various tissues. Collectively, these results support PICN as a promising alternative, combining favorable safety and comparable pharmacokinetics.

Pesticides are well-known harmful substances that cause oxidative stress and testicular dysfunction in both humans and animals, whereas omega-3 fatty acids (ω3FAs) have been demonstrated to possess antioxidant and anti-inflammatory properties. Thus, the primary focus of this investigation was the protective role of (ω3FAs) and their related molecular mechanism in testicular dysfunction induced by acetamiprid plus emamectin benzoate in rats. Rats were divided into four groups: control, omega-3 fatty acids (ω3FA; 300 mg/kg BW), insecticide mixture (Insec Mix; Acetamiprid (30 mg/kg BW) and emamectin benzoate (9 mg/kg BW)), and ω3FA + Insec Mix, respectively. ω3FA was taken orally an hour before insecticide treatment for three weeks daily. The results demonstrated that lipid peroxidation markers and lactate dehydrogenase activity were significantly elevated in rats intoxicated with pesticides; however, enzymatic antioxidants, aminotransferases, phosphatases, and reduced glutathione decreased. Furthermore, notable changes in testicular Bax, Cas-3, Bcl-2, P53, IL-1β, TNF-α, NFkB, Nrf2, hormones, sperm quality, testis structure, and Ki-67 protein expression were detected. Otherwise, ω3FA pre-treatment before insecticide intoxication substantially recovered most of the molecular and biochemical indicators and improved testicular cellular structure. Conclusively, ω3FA was highly effective in mitigating testicular toxicity conferred by acetamiprid and emamectin benzoate insecticides.

Vincristine (VCR) is a common drug used for this purpose. Apilarnil is a substance known for its antioxidant, antidiabetic and chemoprotective properties with positive effects on the reproductive system. In this study, the effects of apilarnil against testicular damage in vincristine-treated rats were investigated. For this purpose, 35 male Sprague-Dawley rats were used in the study. The rats were divided into five groups as control, VCR, APL, VCR + APL 200 mg/kg of body weight and VCR + APL 400 mg/kg of body weight. VCR was administered intraperitoneally between days 1-6 and 9-14, while APL was administered by oral gavage for 14 days. After the study, rats were sacrificed, testicular tissues were removed and examined biochemically and histopathological, and epididymis tissue was used for spermatological analysis. VCR administration induced oxidative stress, endoplasmic reticulum stress, inflammation and apoptosis in testicular tissue, leading to changes in testicular histology and decreased epididymal sperm quality. APL administration, on the other hand, suppressed oxidative stress, apoptosis, ER stress and inflammation while preserving testicular histology and preventing the decrease in epididymal sperm quality. In conclusion, APL has protective effects against the damage caused during chemotherapy.

Male infertility is a multifactorial condition affecting approximately 8%-12% of reproductive-age couples worldwide, with male factors contributing to nearly half of all cases. Traditional treatments often offer limited efficacy, especially in cases involving testicular toxicity, diabetes-related erectile dysfunction, and aging-associated reproductive decline. In recent years, mesenchymal stem cell-derived exosomes (MSC-EXOS) have emerged as a promising cell-free therapeutic approach due to their ability to carry bioactive molecules-such as proteins, lipids, and microRNAs-that modulate inflammation, oxidative stress, apoptosis, and tissue regeneration. This review highlights the pathophysiology of key male reproductive disorders and explores the therapeutic potential of MSC-EXOS in preclinical models. Evidence demonstrates that exosomes from adipose tissue, bone marrow, and umbilical cord MSCs can improve spermatogenesis, restore hormonal balance, enhance vascular function, and repair damaged testicular architecture. While findings are encouraging, challenges remain regarding optimal delivery, dosage, and translation to clinical settings. This review provides the most comprehensive synthesis of preclinical evidence to date demonstrating that mesenchymal stem cell-derived exosomes consistently outperform traditional MSC therapy across multiple male reproductive disorders while offering superior safety and scalability. These findings establish exosomes as a transformative cell-free platform ready for clinical translation in male infertility, warranting further investigation through clinical trials and mechanistic studies.

Fine particulate matter (PM2.5) is increasingly implicated in male reproductive impairment. However, because most research remains acute-focused, delayed, persistent, or progressive post-exposure testicular damage-critical for long-term risk assessment-remains poorly understood. We established a time-resolved rat model to determine whether injury persists or worsens after exposure. Seventy-two male Sprague-Dawley rats were randomized into nine groups (control; vehicle at 24 h, 1, 2, and 4 months; PM2.5 at the same time points) and received intranasal PM2.5 at 5 mg/kg/day for 7 days. We quantified sperm quality and reproductive organ indices, examined testicular histology and ultrastructure, measured serum testosterone, FSH, LH, and E2, profiled inflammatory cytokine mRNAs (IL-1β, IL-6, TNF-α, IFN-γ), assessed germ-cell apoptosis by TUNEL, and evaluated junctional and stress-related proteins (Connexin-43, Occludin, JNK). PM2.5 exposure resulted in sustained declines in sperm concentration and motility, along with increased malformations and testicular and epididymal atrophy that did not recover over the 4-month post-exposure period. Histology showed progressive thinning of the seminiferous epithelium and ultrastructural degeneration. Endocrine disruption was also evident, with reduced testosterone and altered gonadotropins. Mechanistically, PM2.5 exposure maintained elevated IL-1β and IL-6 expression, promoted germ cell apoptosis, and downregulated Connexin-43 and Occludin while exhibiting patterns consistent with activation of the JNK pathway. Together, these findings demonstrate delayed and progressive testicular toxicity after PM2.5 exposure ends and suggest that preserving junctional integrity and targeting JNK may mitigate long-term reproductive harm.

Ganoderma lucidum mitigates oxidative stress and apoptosis in chlorpyrifos‑induced testicular toxicity in male rats.

Azelastine attenuates Cisplatin-induced renal and testicular injury: Involvement of Nrf2/SLC7A11-GPX4 and NCOA4-mediated ferroptosis.

F-53B exposure induced testicular premature aging through ZBP1-mediated programmed necrosis.

The ameliorative effects of L-arginine on testicular and genotoxic toxicity induced by chronic exposure to cadmium chloride in male murine models.

β-caryophyllene mitigates metabolic dysfunction in the testes of gerbils perinatally exposed to BPA.

Empagliflozin beyond antidiabetic effect: Amelioration of cyclophosphamide-induced testicular toxicity in rats: Orchestrating klotho/Nrf-2/PPAR-γ/NF-κB/Bax/Bcl-2 cues.