Testis Toxicity Research Articles

Investigation of the Effects of Selenium Against 4-Nonylphenol-induced Toxicity in Rat Testis.

The study aims to investigate whether selenium (Se) has a protective role against testicular toxicity induced by 4-nonylphenol (4-NP) in rats and reduces oxidative damage. For this purpose, 30 adult male Sprague-Dawley rats (250-300g/90days old) were divided into five equal groups: control, sham control, Se, 4-NP, and 4-NP + Se. The trial lasted 48days, with 4-NP administered at 125mg/kg/day and Se at 0.5mg/kg/day. The general microscopic examination of the testicular tissue involved measuring the diameters of seminiferous tubules, epithelial heights, and the density of stage XIV tubules in sections stained with the triple staining method. Caspase 3 and CX43 expressions were observed immunohistochemically, and the numbers of live-dead and normal-abnormal spermatozoa were recorded. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were determined in blood serum and testicular tissue. At the end of the study, testicular toxicity due to 4-NP was demonstrated cytologically, histologically, histometrically, biochemically, and immunohistochemically. Se showed a positive effect against this toxicity, as evidenced by higher stage XIV tubule density in the 4-NP + Se group, lower caspase 3 levels compared to the 4-NP group, decreased MDA levels, increased SOD levels in serum and testicular tissue, and a higher count of live and normal spermatozoa. When used alone, Se may cause metabolic adverse effects, such as decreased live weight gain, reduced tubule diameter and epithelial height, and increased caspase 3 expression, depending on the dose and duration of use.

Plant Extracts with Antioxidant Properties Ameliorate Lead Toxicity in Rats' Testes

Plant Extracts with Antioxidant Properties Ameliorate Lead Toxicity in Rats' Testes

Cyclophosphamide-induced multiple organ dysfunctions: unravelling of dose dependent toxic impact on biochemistry and histology.

Cyclophosphamide, an immunosuppressive alkylating agent, has been used against breast cancer, lymphoma and myeloid leukemia. Despite various therapeutic uses, its toxic impacts on multiple organs remains to be fully elucidated. This study aimed to investigate dose dependent toxic impact of cyclophosphamide on liver, kidney, brain and testis emphasizing serum and tissue biochemical and histological alterations. Experimental design consisted of five groups of albino rats. Group 1-5 were administered vehicle for five consecutive days. On 6th day, group 1 received vehicle only and termed as control; group 2-5 received cyclophosphamide through intraperitoneal route at the rate of 50, 100, 150 and 200mg/kg dose, respectively. After 24h of the last administration, rats were euthanised; serum and tissue biochemistry; histology, sperm count and its motility were performed. Serological, biochemical and histological indices exhibited dose dependent deviations from their regular status as a marker of toxicity in liver, kidney, brain and testis. Tukey's HSD post hoc test revealed maximum damage in multiple organs with 200mg/kg dose of cyclophosphamide.

Quantitative assessment of Nigella sativa and conjugated silver nanoparticles against hexavalent chromium toxic effects on sperm function

Infertility has been observed as one of the major issues in humans, one known risk factor is heavy metals. The main focus of the present research was to assess the toxic effect of hexavalent chromium (Cr (VI)) on sperm and its mitigation by Nigella sativa seed extract (NS) and its conjugated silver nanoparticles (NS+NP). In the present study, we administered 1.5mg/kg body of Cr (VI) orally in mice for 60 days routinely, to induce toxicity in testes and effect on sperm production and motility in male mice. NS and NS+NP (50mg/kg body weight) were administered to evaluate protective action against Cr (VI). The sperm were analyzed by computer-assisted semen analysis (CASA) and chromium concentration in testicular tissue was measured via the atomic absorption spectrophotometer. The CASA analysis showed that Cr (VI) was directly linked with a decline in sperm concentration, motility, distance, velocity, straightness, and head beat frequency attributes. However, the administration of Nigella sativa seed extract and its green synthesized silver nanoparticles improved sperm concentration, motility, distance, velocity, straightness, and head beat frequency. The chromium content in the testes of Cr-exposed animals significantly increased, which negatively affected sperm parameters. However, Nigella sativa and Nigella sativa conjugated silver nanoparticles appeared to help in the removal of Cr content from testes hence improving the sperm parameters in exposed mice. The decrease in Cr concentration improved sperm quality and quantity, hence, improve male fertility.

Eliminating amoxicillin-induced testes toxicity by Ashwagandha seeds

Eliminating amoxicillin-induced testes toxicity by Ashwagandha seeds

Cel-CS1K: A Celastrol-Chitosan Conjugate for Treating Diet-Induced Obesity.

Celastrol (Cel), extracted from Tripterygium wilfordii Hook, is a potential antiobesity drug, except for its adverse reactions in clinic. In the present study, we synthesized a promising celastrol-chitosan conjugate (Cel-CS1K) and evaluated its antiobesity effect and biological safety in diet-induced obese mice. Cel-CS1K showed higher drug loading (over 10 wt %), good solubility (18-19 mg/mL) in water, slower peak time (Tmax = 4 h), and clearance (T1/2 = 8.97 h) in rats. Cel-CS1K effectively attenuated the cytotoxicity, celastrol-induced apoptosis, and fat accumulation of hepatocytes. Cel-CS1K reduced body weight and dietary amount same as the free Cel but with lower toxicity in blood, liver, and testis. Cel-CS1K improved the glucose homeostasis, HDL-C level, insulin sensitivity, and leptin sensitivity, while it significantly reduced the gene expression levels of LDL-C, TG, and TC in obese mice. Furthermore, the adipose-related gene expression levels provided evidence in support of a role for Cel-CS1K in losing weight by the multimode regulation. Overall, Cel-CS1K provides a translatable therapeutic strategy for the treatment of diet-induced obese humans.

Therapeutic effects of vitamin B17 against anabolic steroid Trenorol induced testicular toxicity, injury, DNA damage and apoptosis in male rats.

Several anabolic androgenic steroids (ASSs) are a group of synthetic molecules derived from testosterone and developed mainly for veterinary use that classed as a Schedule III and sometimes utilized by athletes to enlarge their muscles. Abuse of anabolic androgenic steroids can result in severe organ damage that cannot be repaired. Therefore; the objective of the current investigation was to examine the therapeutic effects of vitamin B17 (VitB17) on the testicular toxicity caused by the anabolic steroid Trenorol in male rats. Rats were randomly assigned into control, VitB17 (50mg/kg b.wt./day, orally), Trenorol (received 10mg/kg b.wt./week, IM) and Trenorol+VitB17 treated groups. At the end of experiment, hormonal assay, semen evaluation, testicular enzymes, and DNA damage were assessed. Besides, the histopathological and immunohistochemical investigations of the P53 expression were performed. Current results revealed that; Trenorol induced significant depletion in relative weights of testis (RWT), total testosterone follicle stimulating hormone (FSH), and luteinizing hormone (LH), sperm count, morphology index, viability, progressive motility, and testicular injury and a significant increase sperm abnormalities, testicular DNA damage and P53 experssions. Treatment of rats with Trenorol+VitB17 decreased the testicular toxicity, sperm parameters, DNA damage and apoptosis. We can conclude that; Trenorol induced toxicity, DNA damage and apoptosis in rat testis and treatments with VitB1 improved these parameters.

Ameliorative effects of L-carnitine as an antioxidant against testicular toxicity induced by AlCl3 in male albino rats.

The goal of this study was to investigate the potential protective effect of L-carnitine (20 mg/kg bw, 1/20 LD 50) against aluminum chloride (AlCl3) on the quality of the male rats' testicles and sperm, as well as to determine whether or not the effects of AlCl3 could be counteracted by using L-carnitine as an antioxidant. Six groups of 36 adult male albino rats (n=6) were randomly formed. In Group I (Gp I), saline injection was given orally as a control. Group II (Gp II) was injected orally with 75 mg/kg body weight of L-carnitine. Group III (Gp III) was given a high dose of L-carnitine (150 mg/kg body weight) orally, while Group IV (G IV) was given a low dose of AlCl3 (20 mg/kg body weight). Group V (Gp V) was given an oral injection of AlCl3 (20 mg/kg) and L-carnitine (75 mg/kg body weight). Group VI (Gp VI) was given AlCl3 at a dose of 20 mg/kg and L-carnitine at a dose of 150 mg/kg body weight for 60 days. The reproductive capacity of each group was assessed. Thus, in addition to histopathological analysis and the comet assay to evaluate sperm DNA deterioration, final body weight, testicular weight change, and sperm analysis were carried out. The findings revealed that AlCl3 caused a significant decrease in final body weight, relative weight of sex organs, sperm concentration, motility and viability, serum testosterone concentration, and a significant increase in sperm abnormalities. Furthermore, AlCl3 caused visible changes in the histological structure of the testis. L-carnitine treatment alleviated the harmful effects of AlCl3, as evidenced histopathologically by a noticeable improvement in testis tissues. When it comes to treating AlCl3-induced reproductive toxicity in male rat testes, L-carnitine shows promise.

Selenium reduces acrylamide-induced testicular toxicity in rats by regulating HSD17B1, StAR, and CYP17A1 expression, oxidative stress, inflammation, apoptosis, autophagy, and DNA damage.

This study investigated the effects of Selenium (Se) on testis toxicity induced by Acrylamide (ACR) in rats. In our study, 50 male adult rats were used, and the rats were divided into five groups; control, ACR, Se0.5 + ACR, Se1 + ACR, and Se1. Se and ACR treatments were applied for 10 days. On the 11th day of the experimental study, intracardiac blood samples from the rats were taken under anesthesia and euthanized. Sperm motility and morphology were evaluated. Dihydrotestosterone, FSH, and LH levels in sera were analyzed with commercial ELISA kits. MDA, GSH, TNF-α, IL-6, and IL-1β levels and SOD, GPx, and CAT, activities were measured to detect the level of oxidative stress and inflammation in rat testis tissues. Expression analysis of HSD17B1, StAR, CYP17A1, MAPk14, and P-53 as target mRNA levels were performed with Real Time-PCR System technology for each cDNA sample synthesized from rat testis RNA. Testicular tissues were evaluated by histopathological, immunohistochemical, and immunofluorescent examinations. Serum dihydrotestosterone and FSH levels decreased significantly in the ACR group compared to the control group, while LH levels increased and a high dose of Se prevented these changes caused by ACR. A high dose of Se prevented these changes caused by ACR. ACR-induced testicular oxidative stress, inflammation, apoptosis, changes in the expression of reproductive enzymes, some changes in sperm motility and morphology, DNA, and tissue damage, and Se administration prevented these pathologies caused by ACR. As a result of this study, it was determined that Se prevents oxidative stress, inflammation, apoptosis, autophagy, and DNA damage in testicular toxicity induced by ACR in rats.

Benzophenone-2 exerts reproductive toxicity in male rats

Benzophenone derivatives such as benzophenone-2 (BP-2) belong to the group of endocrine disrupting compounds (EDCs). Increased exposure to EDCs is considered to be an important factor behind the decline of human fertility. The main aim of the present study was to determine the effect of BP-2 on testicular function specified by sperm analysis, the level of sex hormones and their receptors. Since BP-2 has been shown to activate the immune system, another aim of the research was to verify the hypothesis that the immune system may be contributing to the testis toxicity of this compound and for this purpose changes in macrophage and lymphocyte populations in the testes were determined. BP-2 at a dose of 100mg/kg was administered dermally, twice daily at a dose of 100mg/kg for 4-weeks. It was shown that BP-2 reduced the number and motility of sperm and increased the number of sperm showing morphological changes. By determining the concentration of sex hormones, a significant decrease in testosterone levels and an increase in the blood levels of 17β-estradiol were demonstrated. Similar to the results obtained from the blood samples, testosterone levels in the testes were lowered, which could affect sperm parameters. The effect of BP-2 on lowering testosterone levels and the number of sperm cells may be due to immunoactivation in the testes, because it has been detected that this compound significantly decreased the number of the immunosuppressive resident testicular macrophages (TMs) (CD68-CD163+), but increased pro-inflammatory TMs with monocyte-like properties (CD68+CD163-).

T-2 mycotoxin Induces male germ cell apoptosis by ROS-mediated JNK/p38 MAPK pathway

T-2 mycotoxin, a type A trichothecene toxin that, specifically, causes male and female reproductive toxicity. We evaluated T-2 toxin toxicity in testes from neonatal testes after in vitro tissue cultured. Additionally, current study focuses on the molecular mechanism of toxicity and germ cell damage in GC-1 spermatogonial cells. Mouse testicular fragments were subjected to T-2 toxin (0-20nM) during days 5 of in vitro culture. Testicular germ cell number were reduced and downregulated the expression of corresponding markers depending on the exposure concentration of T-2 toxin; however, Sertoli cell markers and steroidogenic enzyme expression increased when treated with 20nMT-2 toxin. The cell viability decreased, apoptosis increased, and pro-apoptotic protein expression increased in 5-20nMT-2 toxin-exposed spermatogonia. Moreover, T-2 toxin generated reactive oxygen species (ROS) and induced mitochondrial dysfunction, indicating that activation of p38 MAPK signaling triggered by ROS is involved in the apoptotic molecular mechanism of T-2 toxin. T-2 toxin induced the phosphorylation of ERK1/2, c-Jun, JNK/SAPK, p38, and p53, and the subsequent inhibition of AKT phosphorylation. The upregulation of genes related to apoptosis and MAPK/JNK signaling was consistently observed in cells exposed to T-2 toxin. These results indicate that T-2 toxin triggers apoptotic cell death in germ cells through the triggering of ROS-mediated JNK/p38-MAPK signaling pathways.

The Protective Effects of Trametes Versicolor on Arsenic-Induced Male Reproductive Toxicity through Regulation of Oxidative Stress: A Biochemical and Histopathological Survey

Exposure to arsenic is linked to a wide range of diseases, in particular male reproductive toxicities. Trametes versicolor is a traditional medicinal fungus with a remarkable potential for antioxidant activity. The purpose of this study was to examine the ameliorating effects of water and methanol extracts of T. versicolor on arsenic-induced male reproductive toxicities via the abrogation of oxidative stress. The mice were divided as follows: control: normal saline, As: arsenic (15 mg/kg), WE: water extract (400 mg/kg), ME: methanol extract (400 mg/kg), As + WE: arsenic (15 mg/kg) + water extract (100, 200, 400 mg/kg), As + ME: arsenic (15 mg/kg) + methanol extract (100, 200, 400 mg/kg), and positive control: arsenic (15 mg/kg) + vitamin C (500 mg/kg). Animals were treated via the intraperitoneal route. About 24 hr later, the mice were euthanized, and oxidative stress parameters (reactive oxygen species [ROS], lipid peroxidation, glutathione concentration, protein carbonylation, glutathione peroxidase, and superoxide dismutase activity), histopathological changes and sperm parameters (count, motility, and morphology) were examined in the testicular tissue. Arsenic caused significant pathological changes in the testicular tissue and sperm morphology and significantly reduced sperm count and motility. Moreover, arsenic mediated oxidative stress via significant increases in ROS generation, lipid peroxidation, and protein carbonyl content, as well as significant depletion in glutathione concentration and superoxide dismutase and glutathione peroxidase activities. Although, coadministration of water and methanol extracts of T. versicolor at 200 and 400 mg/kg counteracted arsenic-induced oxidative and histopathological damages and improved sperm parameters. Our study indicated that T. versicolor ameliorated arsenic-induced testis toxicity and sperm dysfunction via attenuation of oxidative damage.

Melatonin Ameliorates Cyclophosphamide-Induced Spermatogenesis Disorder by Reducing Pyroptosis

As a chemotherapeutic drug, cyclophosphamide (CP) has a negative impact on male fertility due to its reproductive toxicity. Melatonin (Mel) promotes the male reproductive system and increases testosterone synthesis. This study is aimed at exploring the molecular mechanism of Mel as a protector of male fertility against CP-induced cytotoxicity. A CP toxicity model was established in adult ICR male mice by intraperitoneal injection of 100 mg/kg CP every other day for a week. Protective effects of Mel on the testis from CP-induced damage were evaluated using four groups of ICR male mice that received intraperitoneal injections of normal saline, 100 mg/kg CP, 10 mg/kg Mel, or the same dosage of CP and Mel, respectively. Testis morphology was observed by hematoxylin and eosin (HE) staining. Sperm quality parameters were evaluated, and sperm function was studied by in vitro fertilization (IVF). Proliferation, meiosis, and pyroptosis markers were examined by western blot. Results showed that CP treatment induced testis toxicity in a time-dependent manner with the most severe damage to the testis at two weeks post CP treatment. CP-treated mice showed reduced testicular weight and impaired spermatogenesis by downregulating PCNA and SYCP3, reduced serum testosterone levels, decreased sperm counts and motility, increased seminiferous tubule vacuolization, and oxidative damage to spermatogenic cells. All these effects, apart from testicular weight, could be ameliorated by Mel administration. The IVF experiment revealed that CP treatment reduced the rates of sperm fertilization and blastocyst development, which were also enhanced by Mel. Mel-treated mice also showed increased expression of proliferation-associated protein PCNA and meiosis-associated proteins REC8, STRA8, and SYCP3, which were all reduced by CP. Furthermore, Mel inhibited the pyroptosis of spermatogenic cells by reducing GSDMD and IL18 expression. In conclusion, this study indicated that Mel might protect the testis from CP-induced DNA damage to germ cells through the alleviation of pyroptosis.

Protective Effect of l-Theanine on Cyclophosphamide-Induced Testicular Toxicity in Mice

l-Theanine is the most abundant free amino acid present in tea. Several tea components have been studied for their impact on male fertility, but little is known about the effects of l-theanine. Cyclophosphamide (CP) is an antineoplastic and immunosuppressive agent that reduces fertility in males. In the present study, we evaluated the effect of l-theanine on CP-induced testicular toxicity in male mice. A single dosage of 50 mg/kg saline or CP was administered intraperitoneally over the course of 5 days. Mice were administered l-theanine (80 mg/kg) or saline by gavage for 30 days. Animals were euthanized 24 h after the last l-theanine administration, and the testes were removed for histopathological and transmission electron microscopy analysis. Histological evaluation and transmission electron microscopy showed that administration of l-theanine alleviated CP-induced damage to the testicles, including spermatogonial cells, epithelial cells, seminiferous tubules, and basement membrane. An integrated proteomics and metabolomics investigation of testes revealed that l-theanine therapy substantially affected the quantity of 719 proteins (395 upregulated and 324 downregulated) and 196 metabolites (75 upregulated and 111 downregulated). The top three enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for these proteins and metabolites were purine metabolism, choline metabolism in cancer, and arachidonic acid metabolism. This is the first study to reveal the protective effect of l-theanine on CP-induced testicular toxicity. l-Theanine could be a potential natural active substance for resistance to the testis toxicity induced by CP.

Interleukin-17A knockout or self-recovery alleviated autoimmune reaction induced by fluoride in mouse testis

Fluoride (F) is usually treated as a hazardous material, and F-caused public health problem has attracted global attention. Previous studies demonstrate that interleukin-17A (IL-17A) plays a crucial role in F-elicited autoimmune orchitis and self-recovery reverses F-induced testicular toxicity to some extent, but these basic mechanisms remain unclear. Thus, we established a 180 d F exposure model of wild type (WT) mice and IL-17A knockout mice (C57BL/6 J background), and 60 d & 120 d self-recovery model based on F exposure model of WT mice, and used various techniques like qRT-PCR, western blot, immunohistochemistry and ELISA to further explore the mechanism of F-induced autoimmune reaction, the role of IL-17A in it and the reversibility of F-caused toxicity in testis. The results indicated that F exposure for 180 d caused the decreased sperm quality, the damaged testis histopathology, the enhanced mRNA and protein expression levels of inflammatory cytokines, the changes of autoantibody such as the appearance and increased content of anti-testicular autoantibodies in sera and the autoantibody deposition in testis, the alterations of autoimmune related genes containing the decreased mRNA and protein expressions of AIRE and FOXP3 with an increase of MHCII, and the reduced protein expressions of CTLA4, and the activation of IL-17A signaling cascade like the elevated mRNA and protein expressions of IL-17A, Act1, NF-κB, AP-1 and CEBPβ, and the increased protein expressions of IL-17RC, with a decrease of IκBα. After IL-17A knockout, 29 of 35 F-induced changes were alleviated. In two self-recovery models, all F-caused differences except fluorine concentration in femur were gradually restored in a time-dependent manner. This study concluded that IL-17A knockout or self-recovery attenuated F-induced testicular injury and decrease of sperm quality through alleviating autoimmune reaction which was involved with the activation of IL-17A pathway, the damage of self-tolerance and the enhancement of antigen presentation.

X-box binding protein 1 caused an imbalance in pyroptosis and mitophagy in immature rats with di-(2-ethylhexyl) phthalate-induced testis toxicity

As a widely used plasticizer, di-(2-ethylhexyl) phthalate (DEHP) is known to induce significant testicular injury. However, the potential mechanism and effects of pubertal exposure to DEHP on testis development remain unclear. In vivo, postnatal day (PND) 21 male rats were gavaged with 0, 250, and 500mg/kg DEHP for ten days. Damage to the seminiferous epithelium and disturbed spermatogenesis were observed after DEHP exposure. Meanwhile, oxidative stress-induced injury and pyroptosis were activated. Both endoplasmic reticulum (ER) stress and mitophagy were involved in this process. Monoethylhexyl phthalate (MEHP) was used as the biometabolite of DEHP in vitro. The GC-1 and GC-2cell lines were exposed to 0, 100μM, 200μM, and 400μM MEHP for 24h. Reactive oxygen species (ROS) generation, oxidative stress damage, ER stress, mitophagy, and pyroptosis were significantly increased after MEHP exposure. The ultrastructure of the ER and mitochondria was destroyed. X-box binding protein 1 (XBP1) was observed to be activated and translocated into the nucleus. ROS generation was inhibited by acetylcysteine. The levels of antioxidative stress, ER stress, mitophagy, and pyroptosis were decreased as well. After the administration of the ER stress inhibitor 4-phenyl-butyric acid, both mitophagy and pyroptosis were inhibited. Toyocamycin-induced XBP1 down-regulation decreased the levels of mitophagy and pyroptosis. The equilibrium between pyroptosis and mitophagy was disturbed by XBP1 accumulation. In summary, our findings confirmed that DEHP induced a ROS-mediated imbalance in pyroptosis and mitophagy in immature rat testes via XBP1. Moreover, XBP1 might be the key target in DEHP-related testis dysfunction.

The role of mitochondrial dynamics imbalance in hexavalent chromium-induced apoptosis and autophagy in rat testis

Hexavalent chromium (Cr(VI)) is a ubiquitous environmental pollutant that can cause reproductive toxicity. However, the exact mechanism of Cr(VI)-induced testis toxicity remains largely elusive. This study aims to explore the possible molecular mechanism of Cr(VI)-provoked testicular toxicity. Male Wistar rats were intraperitoneally injected with 0, 2, 4, or 6mg/kg body weight/day of potassium dichromate (K2Cr2O7), respectively, for 5 weeks. The results revealed that Cr(VI)-treated rat testis presented varying degrees of damage in a dose-dependent manner. Concretely, Cr(VI) administration suppressed Sirtuin 1/Peroxisome proliferator-activated receptor-γ coactivator-1α pathway and led to mitochondrial dynamics disorder, along with the elevation of mitochondrial division and the repression of mitochondrial fusion. Meanwhile, the downstream effector of Sirt1, nuclear factor-erythroid-2-related factor 2 (Nrf2), was downregulated, and correspondingly exacerbated oxidative stress. Mitochondrial dynamics disorder and Nrf2 inhibition collectively contribute to abnormal mitochondrial dynamics in testis, which further promotes apoptosis and autophagy, evidenced by dose-dependently increasing the protein levels and gene expressions of apoptosis-related (including Bcl-2-associated X protein, cytochrome c, and cleaved-caspase 3) and autophagy-related (Beclin-1, ATG4B, and ATG5). Collectively, our results demonstrate that Cr(VI) exposure induced testis apoptosis and autophagy by disrupting the balance of mitochondrial dynamics and the oxidation-reduction process in rats.

Impact of Coriander Seeds Extract Against Thyroidectomy Induced Testicular Damage and DNA Replication in Male Rats

An important target organ for thyroid hormone activity is the testis and hypo or hyperthyroidism causes noticeable alterations in testicular function. This study aimed to investigate the therapeutic effect of Coriander Seeds Extract (CSE) against thyroidectomy induced toxicity, oxidative stress, injury, and proliferation in male testes rats. 40 male rats were equally divided into 4 groups [Gp1, control; Gp2, CSE; Gp3, thyroidectomies rats (Thy); Gp4, treated thyroidectomies rats with coriander (Thy + CSE)]. Current results revealed after 3 weeks of thyroidectomy; a significant (p<0.05) elevation in TSH, total T4, serum AST, and serum ALP, non-progressive motility and immotile sperms, testicular MDA, testicular injury, and a significant (p<0.05) reduction in total T3, sexual hormones (testosterone, FSH, LH, and prolactin), sperms parameters (count, morphological index, vitality, total and progressive motility), testicular GSH, testicular SOD, and testicular GST and PCNA expressions when compared with control. Thy + CSE modulates most of changes parameters and recovery the testicular injury. We can conclude that; coriander seed extract could enhance the testis against thyroidectomy produced toxicity and oxidative stress in testes through its positive effects in scavenging free radicals.

Ameliorative effect of ellagic acid and Vitamin C against malathion-induced toxicity in testis of adult Wistar rats.

The pesticide malathion (MT), an organophosphate, is highly neurotoxic and causes cholinergic disorders as well as cytotoxicity, genotoxicity, mutagenicity, carcinogenicityand reproductive toxicity. Our purpose was to study the effect of ellagic acid (EA)and Vitamin C on the testis against MT-induced toxicity in the rats. Thirty-six adult Wistar rats were employed, separated into six groupsand were given treatment for 14 days. The toxicity of MT on the testis was evaluated using a variety of physical parameters,such as mortality rate and body weight, as well as biochemical parameters, such as total protein, total cholesterol, serum glutamic-oxaloacetic transaminaseand serum glutamic-pyruvic transaminase, and haematological parameters, such as counts of red blood cells, haemoglobin (Hb)and white blood cells, as well as mean corpuscular volume, mean corpuscular Hb, and mean corpuscular Hbconcentration. At the end of the experiment, rats were killed and a histological examination of the testis was performed. A sperm count technique and an analysis of sperm motility were used to determine the sperm quality. Biochemical indicators, sperm count, motility, viabilityand morphology were significantly decreased with MT. When compared withMT and the control group, EA and Vitamin C administration significantly increased sperm motility and count (p < 0.05). After receiving EA and Vitamin C, biochemical indicators and histological characteristics are also intensified. The results of the current investigation showthat EA and Vitamin C can both reduce increased levels of biochemical markers and improve pathological alterations in the testis brought on by MT treatment.

Tributyltin chloride (TBTCL) induces cell injury via dysregulation of endoplasmic reticulum stress and autophagy in Leydig cells

Tributyltin chloride (TBTCL), a commonly used antiseptic substance, is commonly found in the environment. Human exposure to TBTCL through the consumption of contaminated seafood, fish, or drinking water has aroused concern. It is well-characterized that TBTCL has multiple detrimental effects on the male reproductive system. However, the potential cellular mechanisms are not fully elucidated. Here, we characterized molecular mechanisms of TBTCL-induced cell injury in Leydig cells, a critical supporter for spermatogenesis. We showed that TBTCL induces apoptosis and cell cycle arrest in TM3 mouse Leydig cells. RNA sequencing analyses revealed that endoplasmic reticulum (ER) stress and autophagy were potentially involved in TBTCL-induced cytotoxicity. We further showed that TBTCL causes ER stress and inhibited autophagy flux. Notably, the inhibition of ER stress attenuates not only TBTCL-induces autophagy flux inhibition but also apoptosis and cell cycle arrest. Meanwhile, the activation of autophagy alleviates, and inhibition of autophagy exaggerates TBTCL-induced apoptosis and cell cycle arrest flux. These results suggest that TBTCL-induced ER stress and autophagy flux inhibition contributed to apoptosis and cell cycle arrest in Leydig cells, providing novel understanding into the mechanisms of TBTCL-induced testis toxicity.