SP-Max-A herbomineral formulation attenuates busulfan-induced oligospermia in mice by preventing loss of reproductive hormones.

SP-Max herbal capsule formulation contains Withania somnifera, Asparagus recemosus, Mucuna pruriens, Chlorophytum arundinaceum, Ipomoea digitata, and Dioscorea bulbifera which are reported in the 'Ayurveda', an Indian Traditional System of medicine as aphrodisiacs. The present study focused on the effect of herbomineral formulation, SP-Max in the treatment of oligospermia. Oligospermia was induced in male Swiss Albino mice by a single intraperitoneal injection of busulfan at a dose of 45 mg/kg. SP-Max herbomineral formulation was given at various doses of 130, 270, and 390 mg/kg for 45 days. Treatment with SP-Max herbomineral formulation at 130, 270 and 390 mg/kg doses significantly improved the sperm count, sperm motility and viability (p < 0.001). SP-Max treatment at a dose of 390 mg/kg significantly prevented the loss of anti-oxidant enzymes in testicular cells. SP-Max prevented the reduction in the level of testosterone, luteinizing hormone, and follicle-stimulating hormone. Histological findings showed that SP-Max treatment prevented degeneration of spermatid, interstitial cells, and Sertoli cells of the testes and also improved epididymal sperm count. High dose of SP-Max treatment i.e 390 mg/kg found to be more effective. Results showed that SP-Max herbomineral formulation is an effective treatment option for oligospermia by decreasing free radical damage to the testes and improving the levels of reproductive hormones.

Tranilast abrogates cisplatin-induced testicular and epididymal injuries: An insight into its modulatory impact on apoptosis/proliferation.

Cisplatin is a chemotherapeutic agent whose therapeutic use is greatly limited by the associated organs' toxicity and particularly, testicular toxicity. Cisplatin-induced testicular damage reported being mediated through mitochondria-mediated apoptosis, inflammation, and oxidative stress. Evidence showed that tranilast (TRN) has the ability to restore the oxidative status and modulate TRAIL/caspase-8 signaling. This led us to hypothesize that TRN could abrogate cisplatin-induced testicular and epididymal injuries via inhibiting oxidative stress and modulating proliferation and TRAIL/caspase-8/cJNK signaling. Cisplatin injection induced oligospermia and abnormalities in testicular and epididymal structure along with impaired oxidative status. TRN administration (100 or 300 mg/kg) for 7 days post-cisplatin injection preserved spermatogenesis and restored testicular and epididymal architecture, but restoration was more so in TRN300 than TRN100. This was in line with the restoration of balanced oxidative status as indicated by the increased total antioxidant capacity, glutathione and superoxide dismutase activity, and the decreased malondialdehyde content in testes (p < 0.05 vs. cisplatin). TRN increased the cell proliferation revealed by the increased expression of proliferating cell nuclear antigen in a dose-dependent manner (p < 0.05 vs. cisplatin) whereas only TRN300 decreased testicular cJNK, TRAIL, and caspase-8 expression (p < 0.05 vs. cisplatin). Moreover, TRN dose-dependently inhibited the pro-inflammatory transcription factor NF-kB and the cytokine TNF-α expressions in testes. In conclusion, TRN300 was more effective than TRN100 in alleviating cisplatin-induced testicular and epididymal injuries and in enhancing spermatogenesis. This curative effect of TRN might be mediated through its antioxidant and anti-inflammatory impacts along with its modulatory impact on cJNK/TRAIL/caspase-8 signaling favoring proliferation rather than apoptosis.

Inhibition of ferroptosis attenuates busulfan-induced oligospermia in mice.

Busulfan is commonly used for cancer chemotherapy, nevertheless it cause male infertility via damaging the germ cells. Therefore, the underlying mechanism should be explored. In the present study, we demonstrated for the first time that ferroptosis was involved in busulfan-induced oligospermia in mice. Mice were given testicular injection of busulfan on both sides at the dose of 4 mg/kg body weight to establish the model of oligospermia. Four weeks later, the results showed that busulfan-treated mice exhibited decreased sperm concentration and motility, along with features of typical ferroptosis in testis, such as increased malondialdehyde (MDA) content and prostaglandin-endoperoxide synthase (PTGS2) mRNA expression, and decreased NADPH content. Inhibition of ferroptosis by ferrostatin-1 (Fer-1) or deferoxamine (DFO) partially alleviated busulfan-induced oligospermia in mice. Additionally, we also revealed that busulfan treatment induced spermatogenic cells ferroptosis by down-regulating nuclear factor-E2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4) expressions, and decreasing iron efflux through reduction of ferroportin 1 (FPN1) expression. Fer-1 or DFO obviously reversed busulfan-induced ferroptosis by increasing Nrf2, GPX4 and FPN1 expressions. Furthermore, after activation of Nrf2 by sulforaphane, sperm concentration and motility in busulfan-treated mice increased, accompanied by enhanced expressions of GPX4 and FPN1. These findings imply that busulfan-induced ferroptosis might be mediated via inhibition of Nrf2-GPX4 (FPN1) signaling pathway, and highlight that targeting ferroptosis serves as a potential strategy for prevention of busulfan-induced damage and male infertility.

Angelica keiskei (Ashitaba) powder and its functional compound xanthoangelol prevent heat stress-induced impairment in sperm density and quality in mouse testes.

Recently, gradual decline in human sperm production has become a serious worldwide concern because it leads to increased rates of infertility. Endocrine disrupters, lifestyle changes, and varicocele, all of which elevate testicular temperature, are thought to be the main causes of this decline. The present study aimed to determine whether the dietary phytochemicals Angelica keiskei (Ashitaba) powder (57.5 mg/kg) and its functional component, xanthoangelol (3 mg/kg), can prevent heat stress-induced impairment in sperm density and quality in mice. Sperm parameters were analyzed 28 days after mice exposure to heat. Supplementation with Ashitaba powder completely prevented heat-induced impairment in sperm parameters, including densities of motile sperms and progressive sperms (> 25 µm/sec), and amplitude of lateral head displacement. Xanthoangelol did not exert a complete protective effect; nevertheless, it significantly prevented heat stress-induced reduction in most parameters. Both Ashitaba powder and xanthoangelol elevated the expression of the widely expressed heat shock proteins (HSPs) Hspa1a and Hsp40 and the antioxidant enzyme glutathione synthase in non-stressed testes. Ashitaba powder significantly prevented heat stress-induced reduction in the expression of Hspa1l and Hspa2, which are highly expressed in the testes and critical for fertility. Our results showed that Ashitaba powder and xanthoangelol protected testicular cells from heat stress, probably by elevating the levels of antioxidant enzymes and HSPs. Supplementation with dietary functional phytochemicals may help prevent heat stress-induced male infertility.

Forskolin ameliorates mancozeb-induced testicular and epididymal toxicity in Wistar rats by reducing oxidative toxicity and by stimulating steroidogenesis.

In the present study, we have tested the beneficial effects of forskolin in protecting the mancozeb-induced reproductive toxicity in rats. Adult male Wistar rats were exposed to either mancozeb (500 mg/kg body weight/day) or forskolin (5 mg/kg body weight/day) or both for 65 days and analyzed for spermatogenesis and steroidogenesis and testicular and epididymal oxidative toxicity. A significant decrease in daily sperm production, epididymal sperm count, motile, viable, and hypo-osmotic swelling-tail swelled sperm was observed in mancozeb-treated rats. The activity levels of testicular 3ß-hydroxysteroid dehydrogenase and 17ß-hydroxysteroid dehydrogenase and circulatory testosterone levels were significantly decreased in mancozeb-treated rats. Exposure to mancozeb resulted in a significant decrease in glutathione levels and superoxide dismutase and catalase activity levels with an increase in lipid peroxidation levels in the testes and epididymis. Coadministration of forskolin mitigated the mancozeb-induced oxidative toxicity and suppressed steroidogenesis and spermatogenesis.

[Protective effect of astaxanthin against epididymal oxidative damagein rats with ornidazole-induced oligoasthenozoospermia].

OBJECTIVE: To investigate the improving effect of astaxanthin (AST) on the sperm quality of rats with ornidazole (ORN)-induced oligoasthenozoospermiaand its action mechanism. METHODS: Forty adult male SD rats were equally randomized into groups A (solvent control), B (low-dose ORN ï¼»400 mg/（kg·d）］), C (high-dose ORN ï¼»800 mg/（kg·d）］), D (low-dose ORN ï¼»400 mg/（kg·d）］ + AST ï¼»20 mg/（kg·d）］), and E (high-dose ORN ï¼»800 mg/（kg·d）］ + AST ï¼»20 mg/（kg·d）］), all treated intragastrically for3 weeks.After treatment, the epididymal tails ononeside was taken for determination of sperm concentration and activity, and the epididymideson the other side harvested for measurement of the activities of GSH-Px, GR, CAT and SOD and the MDA contentin the homogenate. RESULTS: Compared with group A, sperm motilityin the epididymal tail andGSH-Px and SOD activities in theepididymiswere markedly decreased while the MDAcontent significantlyincreased in group B (P<0.05), spermmotility and concentrationin the epididymal tail, testisindex, and the activities of GSH-Px, GR, CAT and SOD in the epididymis were remarkably reduced while theMDA contentsignificantly increased in group C(P<0.05). In comparison with group B, group D showed markedly increased sperm motility (ï¼»45.3±8.7ï¼½% vs ï¼»66.3±8.9ï¼½%, P<0.05) in the epididymal tail and SOD activity in the epididymis (ï¼»116.7±25.3ï¼½ U/mg prot vs ï¼»146.1±23.8ï¼½ U/mg prot, P<0.05), decreased MDA content(ï¼»1.68±0.45ï¼½ nmol/mg prot vs ï¼»1.19±0.42ï¼½ nmol/mg prot, P<0.05).Compared with group C, group Eexhibited significant increases in the weight gained (ï¼»89.0±9.5ï¼½ vs ï¼»99.9±4.1ï¼½ %, P<0.05) and sperm motility (ï¼»17.9±3.5ï¼½% vs ï¼»27.3±5.3ï¼½ %, P<0.05) but a decrease in the content of MDA (ï¼»2.03±0.30ï¼½ nmol/mg prot vs ï¼»1.52±0.41ï¼½ nmol/mg prot, P<0.05). CONCLUSIONS: AST can improve spermquality in rats with ORN-inducedoligoasthenozoospermia, which may be associated with its enhancing effect on the antioxidant capacity of the epididymis.

Lifestyle factors and sperm aneuploidy.

Different environmental and lifestyle factors may interfere with the normal disjunction of sister chromatids/chromosomes during meiosis and may cause aneuploidy. The aim of the study was to examine the association between lifestyle factors and sperm aneuploidy. The study population consisted of 212 healthy men under 45 years of age attending an infertility clinic for diagnostic purposes and who had a normal semen concentration of 20-300×106mL or slight oligozoospermia (semen concentration of 15-20×106/mL). All participants were interviewed and provided a semen sample. Sperm aneuploidy was assessed using multicolor FISH (DNA probes specific for chromosomes X, Y, 18, 13, 21). Results from the study suggest that lifestyle factors are related to sperm aneuploidy. A positive relationship was found between coffee drinking everyday and the lack of chromosome X or Y, as well as coffee drinking 1-6 times per week and additional chromosome 18. Wearing boxer shorts decrease the copy number changes in the whole chromosome 18, the number of additional chromosome 18 and the lack of chromosome 13. Additionally, obesity (BMI 30-40 kg/m²) was positively associated with additional chromosome 21 after being adjusted for potential confounders. These findings demonstrate that changing the men's lifestyle habits may contribute to reduction of the incidence of sperm aneuploidy. It is necessary that men continue to follow sensible health advice concerning excess weight, coffee drinking and wearing tight fitting underwear. As this is the first such study to examine different lifestyle factors and sperm aneuploidy, the results need to be confirmed on larger population.

Enclomiphene citrate stimulates testosterone production while preventing oligospermia: a randomized phase II clinical trial comparing topical testosterone.

OBJECTIVE: To determine the effect of enclomiphene citrate in men with secondary hypogonadism. DESIGN: Phase II clinical trial. SETTING: Community dwelling men making visits to physician offices. PATIENT(S): Men with secondary hypogonadism. INTERVENTION(S): Oral administration of enclomiphene citrate or 1% topical T gel. MAIN OUTCOME MEASURE(S): Luteinizing hormone, FSH, T, and semen analysis. RESULT(S): Treatment with enclomiphene citrate resulted in increased morning serum T, E2, and LH levels similar to those obtained with a topical T gel in men with secondary hypogonadism. Follicle-stimulating hormone and LH were increased with enclomiphene, and sperm counts were conserved. CONCLUSION(S): Enclomiphene citrate reverses the two hallmarks of secondary hypogonadism, namely, low serum total T and low or inappropriately normal LH while preserving sperm production. CLINICAL TRIAL REGISTRATION NUMBER: NCT01270841 (ClinicalTrials.gov Identifier NCT01270841).

Effects of chemotherapy and radiotherapy on spermatogenesis in humans.

Treatment of cancer with chemo- or radiotherapy causes reduction of sperm counts often to azoospermic levels that may persist for several years or be permanent. The time course of declines in sperm count can be predicted by the sensitivity of germ cells, with differentiating spermatogonia being most sensitive, and the known kinetics of recovery. Recovery from oligo- or azoospermia is more variable and depends on whether there is killing of stem cells and alteration of the somatic environment that normally supports differentiation of stem cells. Of the cytotoxic therapeutic agents, radiation and most alkylating drugs are the most potent at producing long-term azoospermia. Most of the newer biologic targeted therapies, except those used to target radioisotopes or toxins to cells, seem to have only modest effects, mostly on the endocrine aspects of the male reproductive system; however, their effects when used in combination with cytotoxic agents have not been well studied.

Effect of Curculigo orchioides on hyperglycemia-induced oligospermia and sexual dysfunction in male rats.

Sustained hyperglycemia is considered as a major cause of sexual and erectile dysfunction in human population. Curculigo orchioides (CO) is considered as a sexual tonic in Ayurvedic system of medicine with potent antioxidant and adaptogenic properties. The aqueous extract of the herb was evaluated for its effectiveness against streptozotocin-induced hyperglycemic stress and subsequent sexual dysfunction due to hyperglycemia in male rats. Six groups with eight male rats in each group were used for this study and the study was carried out for 28 days. The body and organ weights of the animals were recorded. Behavioral analysis of rats was undertaken to observe the effect on mount, ejaculation and intromission (latencies and frequencies) and hesitation time. Blood glucose and serum testosterone levels were determined 28 days past treatment with CO at 100 and 200 mg kg(-1) doses. Glibenclamide and sildenafil citrate were used as positive controls. This deleterious effect of sustained hyperglycemia and associated stress was prominently ameliorated in animals treated with aqueous extract of CO. CO treatment was helpful in ameliorating the damage caused by sustained hyperglycemia evidenced in the principle parameters viz. male sexual behavior, sperm count, penile erection index and seminal fructose content Antioxidant and anabolic activities of the extract under investigation could be a major attribute in preserving the sexual functions in hyperglycemic male rats. The study validates the use of CO in traditional medicine for curing diabetes-induced sexual dysfunction and compromised sexual potency.

The role of lifestyle changing to improve the semen quality in patients with varicocele.

AIM: To evaluate the recovery of semen quality in patients with high grade varicocele without hypotrophy and abnormal semen analysis using a simple lifestyle changing protocol. METHODS: Fifty-two patients were eligible for this study. Two semen sample were collected at baseline and other two after treatment. PROTOCOL: patients had to stop or decrease the number of cigarette per day, reduce the coffee and alcohol consumption, introduce fruits and vegetables in the daily diet and have a normal sexual activity with an abstinence of tree days before semen collection. All the variables and the semen parameters were evaluated and correlated between responders and non-responders. RESULTS: Forty patients (76%) had an improvement of semen quality showing a normal semen analysis following the WHO criteria. The other 12 patients had an improvement of the semen quality but without statistical differences. Smokers and drinkers (for both coffee and alcohol) had lower sperm volume, lower sperm motility and vitality when compared to the others. CONCLUSIONS: The analysis of data collected by the spermiograms showed that semen quality could benefit from lifestyle changing. This finding is important for the management of patients with varicocele, suggesting that lifestyle changing could avoid surgery.

Successful treatment of unilateral cryptorchid boys risking infertility with LH-RH analogue.

INTRODUCTION: Infertility is the primary concern for boys with uni- or bilateral undescended testes. An early and seemingly successful orchiopexy does not improve fertility in a substantial number of cryptorchid males. We confirmed that LH-RH analogue (LH-RHa) treatment induces an increase in and maturation of the germ cells; however, it was uncertain if treatment would improve the chance of fertility later in life. MATERIALS AND METHODS: Thirty unilateral cryptorchid boys, with an average age of 3 years at the time of surgery, were included in the study. Testicular biopsy showed that they had impaired testicular maturation and were therefore at high risk for infertility. Fifteen of the 30 unilateral cryptorchid boys were treated with 10 microg LH-RHa (Buserelin) nasal spray, administered on alternate days for a period of 6 months, following orchiopexy. The control group consisted of 15 cryptorchid boys who had been treated by Schoemakers type of orchiopexy, alone. After puberty, the ejaculates of both groups were analyzed. RESULTS: All males in the untreated group were severely oligospermic, with 20% being azoospermic. In contrast, 86% of the treated ex-cryptorchid males had a sperm concentration within the normal range; this was significantly different from the sperm concentration found in the untreated group (p=0.000008). CONCLUSION: For the first time, we demonstrate that infertility in cryptorchidism can be successfully corrected when suitably treated with a LH-RHa. Sperm parameters normalized following therapy in the majority of cryptorchid males who, untreated, would have remained infertile. This innovative hormonal treatment will have a profound effect on the current recommended surgical treatment of boys with undescended testes.

Successful treatment of unilateral cryptorchid boys risking infertility with LH-RH analogue

INTRODUCTION: Infertility is the primary concern for boys with uni- or bilateral undescended testes. An early and seemingly successful orchiopexy does not improve fertility in a substantial number of cryptorchid males. We confirmed that LH-RH analogue (LH-RHa) treatment induces an increase in and maturation of the germ cells; however, it was uncertain if treatment would improve the chance of fertility later in life. MATERIALS AND METHODS: Thirty unilateral cryptorchid boys, with an average age of 3 years at the time of surgery, were included in the study. Testicular biopsy showed that they had impaired testicular maturation and were therefore at high risk for infertility. Fifteen of the 30 unilateral cryptorchid boys were treated with 10 µg LH-RHa (Buserelin) nasal spray, administered on alternate days for a period of 6 months, following orchiopexy. The control group consisted of 15 cryptorchid boys who had been treated by Schoemakers type of orchiopexy, alone. After puberty, the ejaculates of both groups were analyzed. RESULTS: All males in the untreated group were severely oligospermic, with 20 percent being azoospermic. In contrast, 86 percent of the treated ex-cryptorchid males had a sperm concentration within the normal range; this was significantly different from the sperm concentration found in the untreated group (p = 0.000008). CONCLUSION: For the first time, we demonstrate that infertility in cryptorchidism can be successfully corrected when suitably treated with a LH-RHa. Sperm parameters normalized following therapy in the majority of cryptorchid males who, untreated, would have remained infertile. This innovative hormonal treatment will have a profound effect on the current recommended surgical treatment of boys with undescended testes.

Improvement of oligoasthenozoospermia in epileptic patients on switching anti-epilepsy medication from sodium valproate to phenytoin.

We present two cases of infertile male patients with oligoasthenozoospermia who were receiving anti-epilepsy medication. Complete reversal of the spermatic dysfunction followed by a successful conception was achieved after discontinuation of sodium valproate, suggesting that the drug was responsible for spermatic dysfunction in these individuals.

Prevention of chronic alcohol and nicotine-induced azospermia, sterility and decreased libido, by a novel tri-substituted benzoflavone moiety from Passiflora incarnata Linneaus in healthy male rats.

Excessive long term consumption of alcohol and nicotine have serious detrimental effects upon the libido, fertility, and sperm count in male species. The present work describes the beneficial effects of a novel tri-substituted benzoflavone moiety (BZF) isolated from Passiflora incarnata Linneaus, the phyto-chemical isolation, spectroscopic elucidation, and multifarious biological activities of which have recently been reported by the authors. The BZF moiety has been reported to increase libido, sperm count, and sexual fertility in 2 years old male rats at 10 mg/kg, po dose, in the one of our previous studies. Presently, the BZF moiety has been evaluated against chronic ethanol- and nicotine-induced decrease in libido, sexual fertility and mating efficiency in healthy male rats. The male rats were given ethanol (3 g/kg, po) A, nicotine (2 mg/kg, sc) N, alcohol-nicotine combinations (AN) alone, and also with 10 mg/kg po dose of BZF (concurrent administrations). These treatments were given for 30 days. At the end of treatments, it was observed that rat groups A, N, and AN had no libido (evaluated by mounting behaviour), declined sperm count, and consequently no mating efficiency or fertility (upon pairing with pro-estrus female rats). However, the rats which were given 10 mg/kg BZF along-with nicotine (NP group), alcohol (AP group), and alcohol-nicotine combination (ANP) exhibited significant libido-oriented mounting behaviour, increased sperm count (significantly comparable to the control group), and increased fertilization potential. The rats having decreased sperm count, libido and fertilization potential due to chronic administration of alcohol, nicotine and alcohol-nicotine combinations, i.e., rats of A, N, and AN groups were again subdivided and were given 10 mg/kg BZF for 7 days. This treatment confirmed that BZF speeds up the restoration of sexuality in rats upon cessation of the administration of substances like alcohol, nicotine and alcohol-nicotine combinations, which have severe detrimental effects upon male sexuality, fertility and vigour. BZF, the strongest inhibitor of aromatase enzyme, when administered concurrently with substances like alcohol and nicotine restores sexual virility, libido and vigour in male rats by maintaining the blood-testosterone levels to be high.