Protective efficiency of Ashrasi date palm hydroalcoholic extract against diabetes‐induced testicular toxicity: A biochemical and stereological study

The present study was designed to investigate the protective effects of hydroalcoholic extract of Ashrasi date palm (ADP) on diabetes‐induced testicular injuries. Adult male rats were randomly allocated into five groups (n = 8 in each group): 1: control; 2: diabetic; 3: diabetic + 30 mg/kg of ADP extract; 4: diabetic + 90 mg/kg of ADP extract; and 5: diabetic + 270 mg/kg of ADP extract. Diabetes was induced by a single dose of streptozotocin (55 mg/kg) intraperitoneally. Testicular changes were assessed quantitatively using stereological method followed by measuring antioxidant enzymes including catalase, superoxide dismutase and glutathione peroxidase and serum testosterone level. Malondialdehyde (MDA) and Bcl‐2 expression were also evaluated in tissue samples. Diabetes resulted in significant deleterious alterations in the architecture of testicular tissue, suppressed antioxidant enzymes and testosterone levels and increased lipid peroxidation. The expression of Bcl‐2 was downregulated in diabetic testis and resulted in enhanced apoptosis. Eight weeks of ADP extract treatment especially at higher doses could markedly improve structural changes of testis and restore the antioxidant defence and testosterone levels in testicular tissue. In conclusion, this findings showed that ADP extract can play as a potent antioxidant and can attenuate the adverse effects of diabetes on male reproduction.     

Pituitary-adrenocortical response to surgical stress in male patients

Effects of major surgical stress on the plasma levels of twelve kinds of steroid hormones, ACTH and renin activity, and on the excretion rates of urinary free cortisol and acid labile aldosterone etc. were studied in eleven male patients for seven days following operation. In another groups of patients, ACTH tests were carried out in order to investigate the effect of ACTH on the adrenal steroid hormone production. Also, an in vitro assay of the effect of ACTH on the adrenal tissue was performed. Surgical stress provoked marked increase in plasma levels of cortisol, despite little change in aldosterone levels. The postoperative plasma testosterone concentration showed a profound decrease throughout the observation period. The plasma renin activity reached the highest level on the first postoperative day, when plasma aldosterone was at the lowest level. It was concluded that the postoperative changes in the plasma steroid hormone levels were markedly influenced by other physical and humoral disorders provoked with surgical stress.     

Effect of adrenal steroids on testosterone and luteinizing hormone secretion in the ram

The effects of adrenal steroids on testosterone and LH secretion and changes in serum cortisol levels in response to treatments were studied in the ram. Acute administration of synthetic ACTH (10 micrograms/kg BW) elevated (P less than 0.01) serum cortisol and transiently suppressed (P less than 0.05) serum testosterone and LH. Acute dexamethasone treatment suppressed (P less than 0.01) serum cortisol, testosterone and LH. Administration of vehicle had no effect (P greater than 0.10) on serum hormone levels. These data support the contention that adrenal steroids inhibit testicular endocrine function indirectly by acting at the hypothalamic or pituitary level because both ACTH and dexamethasone treatments suppressed serum LH. To differentiate between hypothalamic and pituitary sites of action, the pituitary and testicular responses to an LHRH challenge (100 micrograms) were examined in rams chronically treated with dexamethasone (5 mg i.m., twice daily for 5 days). This treatment regimen suppressed (P less than 0.01) serum cortisol levels. Compared with controls, basal testosterone levels were suppressed (P less than 0.05) in dexamethasone-treated rams; however, no effect (P greater than 0.10) on the magnitude of the testosterone response to LHRH or on either basal or LHRH-stimulated LH secretion was observed. Thus, although a direct testicular effect cannot be eliminated, these data suggest that, in the ram, adrenal steroids inhibit testicular endocrine function by action at the level of the hypothalamus.     

Chlorella vulgaris ameliorates testicular toxicity induced by deltamethrin in male rats via modulating oxidative stress

This study was carried out to investigate the potential effects of Chlorella vulgaris (CV) on testicular function and oxidant/antioxidant status in normal and deltamethrin‐intoxicated rats. Forty adult male rats were drenched either with normal saline, CV (50 mg/kg), deltamethrin (DM) (3 mg/kg), or CV combined with DM, daily for 8 weeks. At the end of the protocol, the epididymal sperm quality was evaluated and the testicular superoxide dismutase (SOD), catalase enzyme (CAT) and malondialdehyde (MDA), and the serum testosterone levels were estimated. Normal rats treated with CV showed a significant increase in the total sperm number/epididymal tail, testicular SOD, and CAT levels with a significant decrease in the testicular MDA. Deltamethrin intoxication significantly decreased the proportions of motile and live sperm, the testosterone concentration, the testicular SOD and CAT levels, whereas it significantly increased the proportion of abnormal sperm and the testicular MDA. Chlorella vulgaris treatment significantly ameliorated the adverse effects of DM‐intoxication and restored most of the parameters to levels that are comparable to those of the control group. In conclusion, CV administration improved the testicular function of normal rats and ameliorated the effect of severe oxidative stress conditions.     

Preventive effects of Aframomum melegueta extracts on the reproductive complications of propylthiouracil‐induced hypothyroidism in male rat

Recent studies have demonstrated that hypothyroidism is associated with infertility. This work was undertaken to evaluate the protective effects of Aframomum melegueta on testicular functions and fertility of hypothyroid male rats. Male rats were orally treated with propylthiouracil (PTU: 10 mg/kg) in combination with plant aqueous or methanol seed extract (20 and 100 mg/kg) for 56 days. Vitamin E and clomiphene citrate served as positive controls. On day 47 of treatment, each male was mated with two adult females for fertilization potential evaluation. At the end of the treatment, genital sex organ weights, sperm characteristics, testicular histology, oxidative status, plasmatic hormones and fertility potential were evaluated. Results indicated that PTU created hypothyroidism characterised by a significant increase in TSH with reduction of T3 and T4. PTU also lowered genital sex organ weights, sperm count, viability and motility, plasmatic levels of luteinising hormone, follicle‐stimulating hormone and testosterone, and increased prolactin, cholesterol and testicular oxidative stress. Alteration in sperm morphology, testis and epididymis histology, and fertilization potential was also noticed. Co‐administration with A. melegueta extracts successfully reversed PTU‐induced infertility without any effect on thyroid hormones. These results provide evidence that A. melegueta has a protective effect on fertility in hypothyroid condition.     

Corrective role of Eugenia jambolana on testicular impairment in streptozotocin‐induced diabetic male albino rat: An approach through genomic and proteomic study

The present study was conducted to explore the effect of ethyl acetate fraction of hydro‐methanolic (40 : 60) extract of seed of Eugenia jambolana on testicular impairment in diabetic rats. In this respect, biomarkers of oxidative stress, genomics and proteomics in testicular tissue were assessed. Side by side, glycated haemoglobin, serum testosterone, activities of glutamate oxaloacetate transaminase and glutamate pyruvate transaminase in serum, epididymal sperm count including reproductive organosomatic indices were evaluated. Results indicate that a significant recovery (P < 0.05) in the levels of these parameters in fraction‐treated diabetic group in comparison with diabetic control. A significant recovery was noted (P < 0.05) in the expression of Bax and Bcl‐2 gene towards the control after the treatment of said fraction. Histological study also focused a significant recovery (P < 0.05) in the number of different generation of germ cells at stage VII of spermatogenesis in fraction‐treated diabetic group. The said fraction treatment to diabetic rat can recover the activities of serum glutamate oxaloacetate transaminase and glutamate pyruvate transaminase significantly towards the control (P < 0.05). Finally, it may be concluded that ethyl acetate fraction of seed of E. jambolana has a promiseable remedial effect on diabetes‐induced testicular dysfunctions in male rat without inducing any metabolic toxicity.     

Cyclophosphamide‐induced male subfertility in mice: An assessment of the potential benefits of Maca supplement

Effects of Lepidium meyenii (Maca) on cyclophosphamide (CYP)‐induced gonadal toxicity in male mice were investigated. Mice were assigned to six treatment groups: Vehicle control, CYP control, CYP plus oral Maca (500 or 1,000 mg/kg), and oral Maca (500 or 1,000 mg/kg). CYP was administered via the intraperitoneal route (days 1–2), while vehicle or Maca were administered daily for 28 days. On day 28, half of the animals in each group were either sacrificed or paired with age‐matched females for fertility assessment. Plasma testosterone assay, sperm analysis and assessment of tissue antioxidant/morphological status were also carried out. CYP administration was associated with oxidative stress, subfertility and morphometric/morphological indices of gonadal injury, while administration of Maca mitigated CYP‐induced gonadal toxicity and subfertility. This study shows that Maca is beneficial in the mitigation of CYP‐induced male gonadal insufficiency and/or testicular morphological changes; however, further studies will be needed to ascertain its usability for this purpose in humans.     

New aspects of androgens, prolactin, and ACTH interaction in men.

Some endocrine effects of prolactin (PRL), ACTH, and corticosteroids in testicular function were evaluated by measuring, in normal men, the effects of short-term experimental stimulation and suppression of either plasma PRL levels or adrenal function on plasma androgen profile. PRL levels were increased by administration of metoclopramide or sulpiride or suppressed with bromocryptine. Long-acting testosterone (T) was injected at 8 a.m. on one day in a control period and during a 9-day period of metoclopramide administration. PRL increase was accompanied by a rise in plasma 17-hydroxyprogesterone and T, whereas PRL suppression induced an increase in 5 alpha-dihydrotestosterone (DHT) plasma levels. Peripheral converions of T into DHT and androstenedione, noted after T injection, decreased during concomitant metoclopramide administration. Plasma testicular androgen levels were lowered after long-acting ACTH injections as well as after 24-hr cortisol administration, but the metoclopramide-induced PRL increase appeared to prevent the suppressive effects of ACTH on plasma T. A low-dose dexamethasone treatment did not modify testicular androgen levels. Experimentally induced hyperprolactinemia may have a stimulatory effect on testicular androgen secretion as well as a lowering action on 5 alpha reduction and oxidative T metabolism in man. On the other hand, ACTH-induced androgen suppression seems to be mediated through high circulating levels of corticosteroids; furthermore, PRL and corticosteroids might have reciprocal influences that modulate their effects on testicular function.     

Risperidone induced reproductive toxicity in male rats targeting leydig cells and hypothalamic–pituitary–gonadal axis by inducing oxidative stress

Risperidone (RIS), a commonly used drug during a lifetime for the treatment of schizophrenia, causes some adverse effects in the male reproductive system; however, there is no comprehensive reproductive toxicity study of RIS. For this purpose, male rats were administered orally for 1.25, 2.5 and 3 mg/kg RIS for 28 days and the sperm count, motility, morphology, DNA damage and the histological changes in testicular tissue were evaluated. Follicle-stimulating hormone (FSH), luteinising hormone (LH) and serum levels of testosterone, which are the main hormonal regulators of reproduction, and testicular glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA) levels as the indicators of oxidative stress were determined. Normal sperm morphology was decreased in RIS groups and histopathological degeneration occurred in testis tissue dose-dependently. Serum LH levels were not altered; however, FSH and testosterone levels decreased in the high-dose group. Histopathologic examination showed RIS toxicity targeted Leydig cells, which might be associated with impairment of the hypothalamic–pituitary–gonadal (HPG) axis. GSH levels were decreased and MDA levels were increased in the high-dose group which was evaluated as indicators of oxidative stress. In conclusion, RIS caused reproductive toxicity in male rats by inducing oxidative stress and disrupting hormonal regulation.     

Teucrium polium attenuates carbon tetrachloride‐induced toxicity in the male reproductive system of rats

The aim of this study was to investigate the protective effects of Teucrium polium (T. polium) on carbon tetrachloride (CCl₄)‐induced male reproductive system damage. The effects of T. polium and vitamin C (Vit C) on sperm parameters, gonadotrophin and testosterone levels, oxidative status and testis tissue structure were assessed in CCl₄‐treated male rats. CCl₄ caused significant alteration of sperm parameters in epididymal and testicular tissues, a decrease in hormone levels, and a decrease in antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in testicular tissues. A noteworthy increase in malondialdehyde (MDA) level was induced in CCl₄‐treated rats with some histopathological damages on the testes compared with control group. Remarkable ameliorations were observed with respect to all the previous parameters, following the administration of CCl₄ with T. polium, and with vitamin C used as a positive control, when compared with CCl₄ alone. Teucrium polium extracts showed good antioxidant performance, suggesting its protective effect against chemically induced reprotoxicity.     

Preventive effects of Resveratrol against azoxymethane‐induced testis injury in rats

To evaluate the protective effects of Resveratrol (RES) on azoxymethane (AOM)‐induced testicular damage using histopathology and biochemical analyses, 28 male rats were randomly divided into four groups. Groups were control, RES, AOM and ARES. At the end of the 7 weeks, following routine tissue processing procedure, testis sections were stained with haematoxylin–eosin and Masson's trichrome. The blood samples were taken for biochemical analysis of testosterone, total oxidative stress, total antioxidant status and oxidative stress index. Degenerative changes in the seminiferous tubules such as atrophy, loss in the number of germ cells and arrested spermatogenic cell, and increase in the connective tissue of the tunica albuginea in the groups with AOM treatment were found. RES treatment (ARES) reduced the number of affected seminiferous tubules significantly (p < .05) compared to AOM alone. The testosterone levels in AOM group were significantly lower than in the control group (p < .05). The total oxidative stress levels were significantly higher in AOM group compared to control group (p < .05). The total antioxidant status levels in ARES group were significantly higher than in the AOM group (p < .05). This study results suggest that an antioxidant like Resveratrol may be useful for decreasing the harmful effects of azoxymethane.     

Pregabalin administration and withdrawal affect testicular structure and functions in rats

The aim of this prospective experimental study was to investigate the effects of pregabalin (PG) administration and withdrawal on testicular structures and functions in rats. A total of 24 male Wistar rats were divided into two groups (n = 12 each): a control group received normal saline, and PG-treated group received 62 mg kg^-1 day^-1 PG for 2 months. Half the animals of each group were sacrificed for the collection of blood and testicular samples. The remaining animals were bred for another 2 months without treatment before collection of blood and testicular samples. PG administration decreased testosterone and increased luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels versus controls. PG withdrawal led to a decrease in both FSH and LH and an increase in testosterone levels versus saline withdrawal. Compared to controls, PG administration caused degeneration of seminiferous tubules and decreased the number of spermatogenic but increased the number of Leydig cells. After PG withdrawal, these cells showed a rebound reverse. Reduced glutathione levels increased with PG administration while PG withdrawal increased malondialdehyde levels. Conclusion: PG administration affected testicular morphometry, gonadotrophic and sex hormones; however, there was a rebound reversal in all these parameters and a significant oxidative stress in PG withdrawal.     

Protective effects of the hydroalcoholic extract of Fumaria parviflora on testicular injury induced by torsion/detorsion in adult rats

This study was designed to determine the effects of daily oral administration (250 mg/kg) of the hydroalcoholic extract of Fumaria parviflora (FP) for 14 days on the sperm parameters, oxidative stress parameters, serum testosterone levels, expression of Bax and Bcl‐2 genes, and apoptosis index of germ cells after testicular torsion–detorsion (ischaemia–reperfusion, IR) injury model in rats. Twenty‐eight adult male Wistar rats were divided randomly into four groups of seven each: sham operation, torsion–detorsion (TD), TD plus the hydroalcoholic extract FP (TDFP) and only FP without TD application (FP). Testicular torsion was created by rotating the left testis 720° in a counterclockwise direction; then, after 4 hr, detorsion was performed. The Johnson's score, mean seminiferous tubule diameter (MSTD) and height (thickness) of seminiferous tubule epithelium (HST) were significantly increased in TDFP and FP groups as compared to TD group. The gene expression of Bcl‐2, level of serum testosterone hormone and antioxidant parameters—GPx and SOD—were significantly higher in TDFP and FP groups than TD group. The index of apoptosis, the gene expression of Bax and the level of MDA were significantly higher in TD group than TDFP and FP groups. Therefore, F. parviflora could decrease oxidative stress induced by testicular torsion–detorsion.     

Treatment preferences and outcome in male hypogonadotropic hypogonadism: an Indian perspective

This retrospective study assessed treatment preferences and outcome with testosterone or HCG / HCG–FSH combination in Indian male idiopathic hypogonadotropic hypogonadism (IHH) subjects (n = 31) above 18 years of age. 38.7% of IHH study subjects had no fertility plans and chose 3 monthly intramuscular testosterone undecanoate. 73.7% of subjects with fertility plans chose human chorionic gonadotropin (HCG) alone due to cost considerations. Spermatogenesis occurred in 21.4% on HCG alone and 60% of subjects on HCG with follicle‐stimulating hormone (FSH) combination. Treatment failure is higher than published Western rates. FSH and HCG combination regimen is costly but superior to HCG alone. However, treatment failure still persists, suggesting unknown testicular defect in IHH.     

Dose‐ and time‐dependent effects of Garcinia kola seed extract on sexual behaviour and reproductive parameters in male Wistar rats

The aim of the present study was to investigate the effects of a crude extract of Garcinia kola on male sexual function after subchronic and chronic treatment periods at different sublethal doses. Adult male Wistar rats were treated orally with 100, 200 and 400 mg kg^?1 of a 70% ethanolic extract of G. kola daily for 56 days. Sexual behaviour studies were performed on days 28 and 50. At termination on day 56, organ weights, sperm count, reproductive hormone levels and testicular histology were assessed. Subchronic and chronic treatment of normal male rats with G. kola extract resulted in overall increase in components of libido, erection and ejaculation in treated rats – with lower doses being more efficient than the higher dose. There was a slight reduction in some components of sexual behaviour with prolonged time of treatment. G. kola treatment at all doses resulted in increased testicular weights, increased sperm count with no change in motility and increased serum testosterone levels with no change in gonadotropin levels. Gross testicular histology was not affected by treatment. We conclude that G. kola seed extract possesses potent aphrodisiac activity in male albino rats with resultant increase in sperm count and testosterone levels.     

The protective effect of Kombucha against silver nanoparticles-induced toxicity on testicular tissue in NMRI mice

Silver nanoparticles (SNPs) can pass from the cell membrane and testicular blood barrier due to their small size, and by increasing oxidative stress they cause disorder in the male reproductive system. Kombucha is a traditional fermented drink with detoxification and potent antioxidant properties. We aimed to examine the protective effect of Kombucha against the damages due to SNPs on the testis tissue. In this experimental study, NMRI mice were randomly separated into four groups (n = 6), namely control (distilled water), SNPs (500 mg/kg), Kombucha extract (9 ml/kg) and SNPs + Kombucha, and were treated with gavage for 35 days. A significant decrease in testosterone level and total antioxidant capacity, and a significant increase in malondialdehyde concentration was observed in the SNPs group in comparison with the control group. Histological studies on the testis of mice treated with SNPs showed vacuolation, decrease in generational epithelium thickness, seminiferous tubules diameter, testis volume and the number of spermatozoa in lumen of the seminiferous tubule and increase in the volume of interstitial space while the mentioned parameters were improved in the SNPs + Kombucha group compared to the SNPs group. Kombucha reduces the adverse effects of SNPs on testis tissue and improves the function of the male reproductive system.     

Effect of kisspeptin challenge on testosterone and inhibin secretion from in vitro testicular tissue of adult male rhesus monkey (Macaca mulatta)

Kisspeptin expression has been found in gonads but a direct role of kisspeptin in reproduction is not known. The objective of this study was to find a dose and time related effect of kisspeptin on testicular hormones secretion of adult male rhesus monkey (n = 5). Kisspeptin (1, 10, 100, 1000 pm ) was incubated to a culture of testes (100 mg fragments) of male rhesus monkey and medium for hormone (testosterone and inhibin) measurement was collected after 30, 60 and 120 min. 10 IU hCG (180 min) and 50 ng FSH (60 and 120 min) were incubated to the culture for checking testicular cells ability to secrete hormones in vitro. Kisspeptin did not significantly (P < 0.05) increase the testosterone and inhibin levels at any dose. However, one way anova at pooled doses showed an increase in testosterone levels and paired t‐test at pooled doses showed inhibin decrease after 120 min of incubation suggesting an independent effect of time. hCG and FSH significantly (P < 0.05) increased hormone concentration compared to the basal groups. We concluded that kisspeptin has no role in testicular regulation related to testosterone and inhibin release but kisspeptin may have other roles in testicular regulation.     

Protective effects of sinapic acid against cyclophosphamide-induced testicular toxicity via inhibiting oxidative stress,caspase-3 and NF-kB activity in BALB/c mice

Cyclophosphamide (CP), as a chemotherapeutic agent, with the generation of oxidative stress leads to testicular toxicity. Sinapic acid (SA), as a phenylpropanoid compound has therapeutic activities. This research was planned to evaluate the improving effects of SA versus testicular injury induced by CP. Forty-eight mice were distributed into six groups: untreated, SA (5 and 10 mg/kg), CP (200 mg/kg) and CP + SA (5 and 10 mg/kg). SA was administrated for 7 successive days and CP was administered intraperitoneally on the 3rd day of study. On the 10th day of research, testicular toxicity was evaluated by sperm parameters test, tissue (oxidative stress parameters) and serum (testosterone) biochemical, histopathological, and immunohistochemical (Caspase-3 and NF-kB) assays. The findings illustrated that CP induces atypical appearance in tissue structure, disorder of sperm parameters dysfunction, decrease of testosterone, oxidative stress (an increase of MDA and decrease of GSH), apoptosis and inflammation in testicular tissue. SA administration protected testis from oxidative stress and improves testosterone level and structure. Moreover, immunohistochemical findings also showed that SA can inhibit Caspase-3 and NF-kB activity. Data have confirmed that SA could protect testis structure and its functions against CP-induced injury through antioxidant, anti-inflammatory and anti-apoptotic activities.     

Selenium attenuates diclofenac-induced testicular and epididymal toxicity in rats

The adverse effect of diclofenac administration on the male reproductive organ in both humans and rats has been reported. Selenium, a trace element vital in nutrition, plays a significant part in cellular redox homeostasis, including male reproduction. However, the impact of selenium on male reproductive toxicity associated with diclofenac administration is lacking in the literature. The current investigation assessed the modulatory effects of selenium on diclofenac-mediated reproductive toxicity in rats. Rats were treated for fourteen consecutive days, either with diclofenac (10 mg/kg) or co-treated with selenium (0.125 and 0.25 mg/kg) body weight. Sperm parameters, enzymes of testicular function, luteinizing, follicle-stimulating hormone and testosterone were assessed in addition to oxidative stress indices and histopathological changes. Selenium significantly alleviated diclofenac-induced decreases in sperm count and motility, testicular function enzymes and levels of luteinizing hormone and testosterone in serum. Moreover, selenium co-administration at 0.125 and 0.25 mg/kg inhibited the diclofenac-induced decrease of antioxidant enzyme activities and increased oxidative stress parameters—lipid peroxidation, reactive nitrogen and oxygen species—in epididymis and testes of rats. Selenium (0.25 mg/kg) alone ameliorated diclofenac-mediated histological injuries in exposed rats. Collectively, selenium enhanced testicular and epididymal function in diclofenac-treated rats by suppressing nitrosative and oxidative stress in rats.