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Background: Tamoxifen (TAM) is a widely used drug in patients with gynecomastia and breast cancer. TAM exerts its anticancer effects via its antiestrogenic activities. Unfortunately, TAM has been reported to exert gonadotoxic effects on male testes. Therefore, this study was designed to explore the possible associated mechanisms involved in TAM-induced testicular dysfunction and the possible ameliorative effects of omega-3 fatty acids (O3FA). Methodology: Animals were randomly divided into control, O3FA, TAM, and TAM + O3FA. All treatment lasted for 28 days. Results: TAM exposure impaired sperm qualities (count, motility, and normal morphology) and decreased testicular 3ß-HSD and 17ß-HSD. It was accompanied by a decline in serum testosterone and an increase in estradiol, luteinizing and follicle-stimulating hormones. These observed alterations were associated with an increase in testicular injury markers, oxido-inflammatory response, and mitochondria-mediated apoptosis. These observed alterations were ameliorated by O3FA treatments. Conclusions: O3FA ameliorated TAM-induced testicular dysfunction in male Wistar rats by modulating XO/UA and Nrf2/NF-kb signaling and cytochrome c-mediated apoptosis in TAM-treated rats.

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BACKGROUND: Testicular toxicity is a complication of cisplatin therapy and it limits its use. Since cisplatin-induced testicular damage is mediated by inflammation and oxidative stress, evaluation of the protective role of antioxidant and anti-inflammatory molecules such as micronized purified flavonoid fraction (Daflon®) is pertinent. AIM: Therefore, this study investigated the mitigating effect of daflon against cisplatin-induced testicular toxicity. Also, the impact of daflon on Nrf2/HO-1 and TLR4/NF-kB pathways, which are key pathways in cisplatin toxicity, was explored. MATERIALS AND METHODS: After 2 weeks of acclimatization, 20 male albino Wistar rats were allotted at random into 4 equal groups; control, daflon-treated, cisplatin-treated, and cisplatin+daflon-treated. RESULTS: Daflon significantly restored cisplatin-induced reductions in body weight (112.20±9.01 vs. 129.60±5.68, P= 0.0175), body weight gain (-39.80±9.52 vs. -16.80±16.53, P= 0.0154), and testicular weight (1.69±0.08 vs. 1.95±0.13, P= 0.0980) and alterations in testicular histology. In addition, daflon abrogated cisplatin-induced rise in testicular CK (55.53±2.77 vs. 37.40±3.29, P< 0.0001) and LDH (74.52±3.20 vs. 65.89±2.08, P= 0.0009) activities, and lactate content (180.50±4.19 vs. 166.20±2.78, P< 0.0001). Also, daflon alleviated cisplatin-induced suppression of GnRH (5.09±0.60 vs. 10.17±0.51, P< 0.0001), LH (1.33±0.07 vs. 2.77±0.13, P< 0.0001), FSH (0.51±0.10 vs. 1.82±0.09, P< 0.0001), and testosterone (2.39±0.11 vs. 4.70±0.33, P< 0.001) as well as lowered sperm quality. More so, daflon attenuated cisplatin-induced testicular oxidative stress, inflammation, and apoptosis evidenced by daflon-driven suppression of MDA (14.16±0.66 vs. 9.22±0.52, P< 0.0001), TNF-α (79.42±5.66 vs. 54.13±3.56, P< 0.0001), IL-1ß (8.63±0.41 vs. 3.37±0.43, P< 0.0001), IL-6 (6.87±0.48 vs. 3.67±0.32, P< 0.0001), and caspase 3 activity (4.20±0.26 vs. 0.72±0.23, P< 0.0001) and DNA fragmentation (34.60±3.05 vs. 17.20±3.19, P< 0.0001), and upregulation of GSH level (0.07±0.03 vs. 0.36±0.03, P< 0.0001), and GPx (5.96±0.46 vs. 11.88±1.05, P< 0.0001), GST (5.16±0.71 vs. 11.50±0.81, P< 0.0001), SOD (1.29±0.15 vs. 2.81±0.29, P< 0.0001), and catalase activities (6.18±0.69 vs. 10.71±0.74, P< 0.0001). Furthermore, daflon upregulated testicular Nrf2 expression (40.25±2.65 vs. 66.62±4.01, P< 0.0001) and HO-1 (4.18±0.56 vs. 8.79±0.55, P< 0.0001) activity but downregulated TLR4 (11.63±0.89 vs. 7.23±0.43, P< 0.0001) and NF-kB levels (113.20±3.36 vs. 78.22±3.90, P< 0.0001) in cisplatin-treated rats. CONCLUSION: Collectively, the ameliorative effect of daflon on cisplatin-induced testicular toxicity is associated with inhibition of oxidative stress and TLR4/NF-kB-mediated inflammatory pathways and activation of Nrf2/HO-1 signaling.

Asunto(s)

Cisplatino , Factor 2 Relacionado con NF-E2 , FN-kappa B , Ratas Wistar , Transducción de Señal , Testículo , Receptor Toll-Like 4 , Animales , Masculino , Cisplatino/efectos adversos , Factor 2 Relacionado con NF-E2/metabolismo , Testículo/efectos de los fármacos , Testículo/metabolismo , Testículo/patología , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Ratas , Diosmina/farmacología , Estrés Oxidativo/efectos de los fármacos

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This study aims to investigate the effect of arsenic exposure on urinary levels of arsenic metabolites, semen parameters, and testosterone concentrations. A systematic comprehensive literature search was conducted up till 31st January 2024 using Embase, MEDLINE/Pubmed, and Scopus. This study adopted the Population Exposure Comparator Outcome and Study Design (PECOS) framework. Four studies with a total of 380 control subjects and 347 exposed men were included. Arsenic exposure significantly increased urinary levels of total arsenic (Mean Difference (MD) - 53.35 [95 % Confidence Interval (CI): - 100.14, - 6.55] P= 0.03), and reduced primary arsenic methylation index (PMI) (MD 0.22 [95 % CI: 0.14, 0.31] P< 0.00001), semen volume (MD 0.30 [95 % CI: 0.05, 0.54] P= 0.02) and total testosterone (MD 0.48 [95 % CI: 0.23, 0.73] P= 0.0002). In addition, arsenic exposure marginally reduced sperm concentration (MD 25.04 [95 % CI: - 45.42, 95.50] P= 0.49) and total sperm motility (MD 22.89 [95 % CI: - 14.15, 59.94] P= 0.23). The present meta-analysis demonstrates that arsenic exposure lowers semen quality and testosterone levels. Since the general human population is exposed to arsenic occupationally or domestically, adequate strategic measures should be put in place to limit arsenic exposure in an attempt to preserve semen quality. In addition, studies investigating interventions that may inhibit the bioaccumulation of arsenic in men who are exposed are recommended.

Asunto(s)

Arsénico , Análisis de Semen , Testosterona , Arsénico/orina , Humanos , Masculino , Testosterona/orina , Exposición a Riesgos Ambientales , Semen/efectos de los fármacos , Motilidad Espermática/efectos de los fármacos , Contaminantes Ambientales/orina

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Background: Pyrethroids are natural organic compounds extracted from flowers of pyrethrums and commonly used as domestic and commercial insecticides. Although it is effective in insect and parasitic control, its associated toxicity, including spermotoxicity, remains a challenge globally. Currently, the available reports on the effect of pyrethroids on semen quality are conflicting, hence an evaluation of its detrimental effect is pertinent. This study conducts a detailed systematic review and meta-analysis of the effects of pyrethroids on sperm quality. Materials and methods: The present study was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using a pre-defined strategic protocol, an internet search was done using combined text words. The criteria for eligibility were selected based on Population, Exposure, Comparator, Outcome, and Study Designs (PECO) framework, and relevant data were collected. Appraisal was done using The Office of Health Assessment and Translation (OHAT) tool for the evaluation of the Risk of Bias and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group guidelines for the certainty of evidence. A quantitative meta-analysis was conducted with the Review Manager (RevMan). Results: Only 12 out of the 4, 050 studies screened were eligible for inclusion in this study. The eligible studies were from China (4), Japan (3), Poland (3), and United States (2). All the eligible studies were cross-sectional. A total of 2, 050 male subjects were included in the meta-analysis. Pyrethroid exposure significantly reduced sperm motility. Region-stratified subgroup analyses revealed that pyrethroid significantly reduced sperm motility among men in Poland and United States, and decreased sperm count among men in Japan. Pyrethroid exposure also reduced sperm concentration among men in Poland but increased sperm concentration among men in the United States. Conclusion: Although the study revealed inconsistent evidence on the detrimental effect of pyrethroids on semen quality, the findings showed that pyrethroids have deleterious potentials on sperm motility, count, and concentration. Studies focusing on the assessment of semen quality in pyrethroid-exposed men, especially at specific varying levels of exposure, and employing prospective cohort studies or controlled cross-sectional designs are recommended.

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AIMS: The aim of this study was to investigate the potential antioxidant, anti-inflammatory, and sperm function-preserving properties of sodium acetate (ACE), a histone deacetylase (HDAC) inhibitor, in a rat model of testicular torsion/detorsion (T/D). MAIN METHODS: Littermate Wistar rats of identical weight were subjected to sham surgery or testicular T/D by rotating the left testis at 720° around its axis along the spermatic cord clockwise and fixing it in this position for two and a half hours. 1 h before detorsion, T/D + ACE-treated rats were treated with ACE (200 mg/kg/day, per os) while T/D rats were vehicle-treated by administering 0.5 mL of distilled water. After 72 h, animals were euthanized, and the left testes were harvested for bio-molecular and histological analysis. KEY FINDINGS: Acetate administration attenuated T/D-induced rises in serum and testicular HDAC and testicular xanthine oxidase, uric acid, MDA, GSSG, MPO, TNF-α, IL-1ß, IL-6, NFkB, HIF-1α, and VCAM-1. In addition, acetate treatment alleviated T/D-induced decline in sperm quality (count, motility, viability, and normal morphology) and testicular 3ß-HSD, 17ß-HSD, testosterone, GSH, GSH/GSSG, SOD, catalase, GPx, GST, Nrf2, and HO-1. Furthermore, acetate prevented T/D-distorted testicular histoarchitecture and spermatogenic germ cell loss. SIGNIFICANCE: Sodium acetate during the post-ischaemic phase of testicular T/D may be beneficial in preventing I/R injury and maintaining fertility.

Asunto(s)

Ratas Wistar , Daño por Reperfusión , Acetato de Sodio , Torsión del Cordón Espermático , Testículo , Masculino , Animales , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Daño por Reperfusión/patología , Daño por Reperfusión/metabolismo , Testículo/efectos de los fármacos , Testículo/patología , Testículo/metabolismo , Ratas , Torsión del Cordón Espermático/tratamiento farmacológico , Torsión del Cordón Espermático/metabolismo , Torsión del Cordón Espermático/complicaciones , Torsión del Cordón Espermático/patología , Acetato de Sodio/farmacología , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/farmacología , Espermatozoides/efectos de los fármacos , Espermatozoides/patología , Inhibidores de Histona Desacetilasas/farmacología

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This study explored the effect of intestinal ischaemia/reperfusion (I/R) on cardiorenal tissues. The involvement of xanthine oxidase/uric acid/NF-kB signaling in intestinal I/R was also investigated. In addition, the possible protective effect of glutamine was also evaluated. Twenty-four male Wistar rats were acclimatized and then randomly assigned to four groups (n = 6); sham-operated, glutamine-treated rats (GLUT), I/R, and I/R + GLUT. The sham-operated rats were sham-operated and received 0.5 mL of distilled water, GLUT rats were sham-operated and had 1 g/kg b.w. of glutamine, I/R animals had an intestinal I/R procedure and received 0.5 mL of distilled water, and the I/R + GLUT rats had an intestinal I/R procedure and also received 1 g/kg b.w. of glutamine. Treatments were daily and per os. Glutamine attenuated intestinal I/R-induced rise in intestinal and cardiorenal activities of creatinine kinase and lactate dehydrogenase and lactate level. More so, glutamine alleviated I/R-induced rise in malondialdehyde, xanthine oxidase, uric acid, myeloperoxidase, NF-kB, TNF-α, IL-1ß, caspase 3 activity, and DNA fragmentation. Furthermore, glutamine suppressed I/R-induced decline in GSH levels and SOD and catalase activities. Moreover, glutamine improved intestinal, cardiac, and renal histology in animals subjected to intestinal I/R.

Asunto(s)

Glutamina , Transducción de Señal , Ácido Úrico , Xantina Oxidasa , Animales , Masculino , Ratas , Traslocación Bacteriana/efectos de los fármacos , Caspasa 3/metabolismo , Glutamina/farmacología , Glutamina/metabolismo , Inflamación/metabolismo , Inflamación/tratamiento farmacológico , Interleucina-1beta/metabolismo , Intestinos/efectos de los fármacos , Intestinos/patología , Riñón/metabolismo , Riñón/efectos de los fármacos , Riñón/patología , Malondialdehído/metabolismo , FN-kappa B/metabolismo , Ratas Wistar , Daño por Reperfusión/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/patología , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Ácido Úrico/metabolismo , Xantina Oxidasa/metabolismo

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The influence of gut microbiota on physiological processes is rapidly gaining attention globally. Despite being under-studied, there are available data demonstrating a gut microbiota-gonadal cross-talk, and the importance of this axis in reproduction. This study reviews the impacts of gut microbiota on reproduction. In addition, the possible mechanisms by which gut microbiota modulates male and female reproduction are presented. Databases, including Embase, Google scholar, Pubmed/Medline, Scopus, and Web of Science, were explored using relevant key words. Findings showed that gut microbiota promotes gonadal functions by modulating the circulating levels of steroid sex hormones, insulin sensitivity, immune system, and gonadal microbiota. Gut microbiota also alters ROS generation and the activation of cytokine accumulation. In conclusion, available data demonstrate the existence of a gut microbiota-gonadal axis, and role of this axis on gonadal functions. However, majority of the data were compelling evidences from animal studies with a great dearth of human data. Therefore, human studies validating the reports of experimental studies using animal models are important.

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Microbioma Gastrointestinal , Microbiota , Animales , Masculino , Femenino , Humanos , Sistema Inmunológico , Reproducción , Citocinas

RESUMEN

INTRODUCTION: Disruption of intestinal histoarchitecture and intestinal dysmotility is critical to intestinal ischemia/reperfusion (IR) injury and xanthine oxidase (XO)/uric acid (UA) signaling and increased lactate generation have been reported to play a role. More so, glutamine treatment has been demonstrated to inhibit XO/UA signaling. However, the role of glutamine in intestinal IR injury-induced intestinal dysmotility and the associated mechanisms of action are unclear. Therefore, this study was to investigate the mechanisms underlying the role of glutamine in intestinal IR injury. METHODS: Forty male Wistar rats were acclimatized for two weeks and then randomized into four groups. The sham-operated, glutamine-treated, intestinal IR, and IR + glutamine groups. RESULTS: Glutamine therapy attenuated the IR-induced increase in intestinal weight, disruption of intestinal histoarchitecture, and intestinal dysmotility. In addition, glutamine ameliorated IR-induced intestinal oxidative stress (increased malondialdehyde, reduced glutathione and superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, and glucose-6-phosphate dehydrogenase activities), inflammation (increased TNF-α and IL-1ß), and apoptosis (increased caspase three activity). These events were accompanied by glutamine alleviation of IR-induced upregulation of intestinal nuclear factor kappa B, XO/UA, and lactate generation. CONCLUSIONS: In conclusion, XO/UA signaling and lactate levels are key factors in IR-induced intestinal injury and dysmotility, and glutamine-mediated XO/UA/lactate modulation may attenuate IR-induced intestinal injury and dysmotility.

Asunto(s)

Enfermedades Intestinales , Daño por Reperfusión , Ratas , Animales , Masculino , Ratas Wistar , Ácido Úrico , Xantina Oxidasa/metabolismo , Glutamina , Ácido Láctico , Regulación hacia Abajo , Estrés Oxidativo , Daño por Reperfusión/prevención & control

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Infertility is a growing challenge globally with emerging risk factors. There are effective laboratory tests to evaluate infertility in humans, nevertheless, some measures, especially histopathological evaluations, are invasive due to the pain inflicted when accessing the reproductive organs and obtaining samples; hence, their relevance may be limited in humans. However, these histopathological evaluations provide essential information on the etiopathogenesis of infertility and the likely mechanisms of action of potential therapeutic candidates. Also, non-invasive methods are available, such as the assay of testosterone in the blood and semen analysis, both of which are predictors of testicular functions. This review provides detailed information on the available histopathological investigations of infertility, such as qualitative and quantitative histopathological assessments of gonadal tissues, specific cell counts, and sperm morphology characterization, with a focus on the procedures, interpretation, and pathophysiological basis. Data from the literature revealed that histopathological examinations of the reproductive organs, as well as spermatozoa, are useful in understanding the pathogenesis of incident infertility. Histopathological evaluation may range from basic hematoxylin and eosin stains to some special stains. Also, histopathological findings (such as spermatogenic cells and planimetric variables, like seminiferous tubule diameter and theca cell and corpus luteum thickness) may be quantified and analyzed for comparison. Some skill is required for these investigations, which may be a limiting factor; however, they are important tools in translational medicine.

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Introduction: Although, codeine has been demonstrated to lower sperm quality; the effects of maternal and prepubertal codeine exposure on male offspring is yet to be reported. In addition, the effect of arginine on codeine-induced decline in sperm quality has not been explored. This study investigated the impact of maternal and prepubertal codeine exposure on spermatogenesis and sperm quality in F1 male Wistar rats to study the effect that codeine may have during recreational use in humans. Also, the effect of arginine supplementation on codeine-induced alteration in spermatogenesis and sperm quality was evaluated. Methods: Female rats were treated with either 0.5 ml distilled water or codeine orally for eight weeks, and then mated with male rats (female:male, 2:1). The F1 male offsprings of both cohorts were weaned at 3 weeks old and administered distilled water, codeine, arginine, or codeine with arginine orally for eight weeks. Results: Prepubertal codeine exposure in rats whose dams (female parents) were exposed to codeine delayed puberty and reduced the weight at puberty. Prepubertal codeine exposure exacerbated maternal codeine exposure-induced reduced total and daily spermatid production, sperm count, sperm motility, and normal sperm form, as well as impaired sperm plasma membrane integrity and increased not intact acrosome and damaged sperm DNA integrity. These perturbations were accompanied by a decrease in mRNA levels encoding spermatogenic genes, testicular testosterone and androgen receptor (AR) concentrations, and upregulation of sperm 8-hydroxydeoxyguanosine (8OHdG). Prepubertal arginine supplementation mitigated codeine-induced alterations. Discussion: This study provides novel experimental evidence that maternal and prepubertal codeine exposure reprogramed spermatogenesis and sperm quality of male FI generation by decreasing mRNA levels encoding spermatogenic genes and AR via oxidative stress-mediated signaling, which was abrogated by prepubertal arginine supplementation.

Asunto(s)

Codeína , Infertilidad Masculina , Humanos , Masculino , Femenino , Ratas , Animales , Codeína/efectos adversos , Codeína/metabolismo , Ratas Wistar , Maduración Sexual , Motilidad Espermática , Semen , Espermatozoides , Espermatogénesis/fisiología , Infertilidad Masculina/inducido químicamente , Agua/metabolismo

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Although psychoactive drugs have their therapeutic values, they have been implicated in the pathogenesis of male infertility. This study highlights psychoactive drugs reported to impair male fertility, their impacts, and associated mechanisms. Published data from scholarly peer-reviewed journals were used for the present study. Papers were assessed through AJOL, DOAJ, Google Scholar, PubMed/PubMed Central, and Scopus using Medical Subjects Heading (MeSH) indexes and relevant keywords. Psychoactive drugs negatively affect male reproductive functions, including sexual urge, androgen synthesis, spermatogenesis, and sperm quality. These drugs directly induce testicular toxicity by promoting ROS-dependent testicular and sperm oxidative damage, inflammation, and apoptosis, and they also suppress the hypothalamic-pituitary-testicular axis. This results in the suppression of circulating androgen, impaired spermatogenesis, and reduced sperm quality. In conclusion, psychoactive drug abuse not only harms male sexual and erectile function as well as testicular functions, viz., testosterone concentration, spermatogenesis, and sperm quality, but it also alters testicular histoarchitecture through a cascade of events via multiple pathways. Therefore, offering adequate and effective measures against psychoactive drug-induced male infertility remains pertinent.

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Andrógenos , Infertilidad Masculina , Masculino , Humanos , Andrógenos/metabolismo , Semen , Testículo/metabolismo , Espermatogénesis , Infertilidad Masculina/etiología , Fertilidad , Psicotrópicos/efectos adversos , Psicotrópicos/metabolismo

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AIM: The present study evaluated the effect of lead exposure with and without zinc therapy on male sexual and erectile function. METHODS: Twenty male Wistar rats were randomly assigned into four groups; the control, zinc-treated, lead-exposed, lead + zinc-treated groups. Administrations were per os daily for 28 days. RESULTS: Zinc co-administration significantly improved absolute and relative penile weights and the latencies and frequencies of mount, intromission, and ejaculation in lead-exposed rats. Also, zinc ameliorated lead-induced reductions in motivation to mate and penile reflex/erection. These findings were accompanied by attenuation of lead-induced suppression of circulating nitric oxide (NO), penile cyclic guanosine monophosphate (cGMP), dopamine, serum luteinizing hormone, follicle-stimulating hormone, and testosterone. In addition, zinc alleviated lead-induced upregulation of penile activities of acetylcholinesterase and xanthine oxidase (XO), and uric acid (UA) and malondialdehyde (MDA) levels. Furthermore, zinc ameliorated the lead-induced decline in penile nuclear factor erythroid 2-related factor 2 (Nrf2) and reduced glutathione (GSH) levels, and catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) activities. CONCLUSION: This study revealed that co-administration of zinc improves lead-induced sexual and erectile dysfunction by suppressing XO/UA-driven oxidative stress and upregulating testosterone via Nrf2-mediated signaling.

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Disfunción Eréctil , Testosterona , Masculino , Ratas , Animales , Humanos , Zinc/uso terapéutico , Disfunción Eréctil/inducido químicamente , Disfunción Eréctil/tratamiento farmacológico , Acetilcolinesterasa , Factor 2 Relacionado con NF-E2 , Ratas Wistar , Ácido Úrico

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The Fat Sand Rat (Psammomys obesus, P. obesus) is a diurnal herbivore and phytophage, with seasonal reproductive behavior. The sexually active phase lasts from autumn to early spring and the sexually inactive phase from late spring to summer. In the past years, P. obesus has gained much attention as an animal model in biological and clinical research. It is a suitable model for diet-induced insulin resistance, non-insulin-dependent diabetes mellitus and obesity studies. In addition, the seasonal reproduction of P. obesus is gaining more and more attention. The current paper aims to review and sum up the progress in the understanding of the reproductive anatomo-histo-physiology of Psammomys obesus, in order to facilitate future research in this area and to expose further perspectives for researchers.

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Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Animales , Gerbillinae , Obesidad , Dieta

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BACKGROUND: Although codeine has been reported to enhance sexual activity by improving penile reflexes, it has been shown to impair fertility indices. Also, codeine impairs ovarian steroidogenesis and folliculogenesis. Nonetheless, whether or not codeine exerts an epigenetic effect remains unclear. On the other hand, arginine has been speculated to enhance penile reflexes by upregulating NO/cGMP Signaling. AIM: The study evaluated the effect of maternal codeine exposure and prepubertal codeine and arginine treatments on F1 male sexual function and fertility indices, as well as the outcome of F2 progenies. In addition, the epigenetic programming mechanism was also explored. METHODS: Forty three-week-old female rats were randomized into two groups (n = 20 rats/group); the control that received 0.5 ml of distilled water and the codeine-treated that received 5 mg/kg of codeine via gavage for eight weeks. Afterward, the female rats were paired for mating with sexually mature male rats. Rats were maintained on their pre-pregnancy treatments throughout pregnancy and lactation. FI progenies from each cohort (control and codeine-treated cohorts) were weaned at three weeks and randomized into four groups; the control, codeine-treated, L-arginine-treated (300mg/kg), and codeine + L-arginine-treated (n = 10 rats/group). Administration commenced a week post-weaning and lasted for eight weeks via gavage. KEY FINDINGS: Maternal codeine exposure did not alter body weight, but significantly reduced anogenital distance and anogenital index of F1 male offspring. Also, maternal codeine delayed preputial membrane separation, impaired male sexual competence, and penile reflexes of F1 male offsprings. These were associated with reduced dopamine, gonadotropins, and testosterone levels as well as suppressed expression of androgen receptor mRNA. In addition, maternal codeine downregulated NO/cGMP signaling, impaired fertility indices, and reduced the litter size, weight, and survival of F2 progenies. These alterations were observed to be aggravated by prepubertal codeine exposure but improved by prepubertal arginine treatment. SIGNIFICANCE: In conclusion, codeine programmed sexual dysfunction by suppressing the levels of dopamine and testosterone, as well as repressing the expression of androgen receptor mRNA. In addition, codeine-induced epigenetic reprogramming was expressed in the F2 offsprings as reduced litter size and weight, and survival rate. Notably, these observations were worsened by prepubertal codeine exposure, but dampened by prepubertal arginine treatment.

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Codeína , Receptores Androgénicos , Animales , Arginina , Codeína/farmacología , GMP Cíclico , Dopamina , Femenino , Masculino , Embarazo , ARN Mensajero , Ratas , Testosterona , Regulación hacia Arriba

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Ethnopharmacological relevance: Oxidative stress is a key player in intestinal ischemia/reperfusion (I/R) injury (IIRI) with a tendency to trigger systemic inflammatory response, resulting in progressive distal organ injury. To date, the role of Bax/caspase 3 signaling in IIRI has not been reported. Furthermore, the discovery of a safe and effective drug remains pertinent in improving the outcome of IIRI. Therefore, this study investigated the role of Bax/caspase 3 signaling in intestinal I/R-induced intestinal and hepatic injury. In addition, the protective effect and possible associated mechanism of action of methanolic Phyllanthus amarus leaf extract (PA) against intestinal I/R-induced intestinal and hepatic injury were evaluated. Materials and methods: Fifty male Wistar rats were randomized into five groups (n = 10). The sham-operated group was received 0.5 mL of distilled water for seven days prior to the sham surgery, while the IIRI, febuxostat (FEB) + IIRI, low-dose PA (LDPA) + IIRI, and high-dose PA (HDPA) + IIRI groups underwent the I/R procedure. In addition to the procedure, IIRI, FEB + IIRI, LDPA + IIRI, and HDPA + IIRI received 0.5 mL of distilled water, 10 mg/kg of febuxostat, 200 mg/kg of PA, and 400 mg/kg of PA, respectively, for seven days prior to the I/R procedure. Results: Administration of methanolic Phyllanthus amarus leaf extracts attenuated the intestinal I/R-induced rise in intestinal and hepatic injury markers, malondialdehyde, nitric oxide, TNF-α, IL-6, and myeloperoxidase activities. In addition, Phyllanthus amarus ameliorated I/R-induced suppression of reduced glutathione, thiol and non-thiol proteins, and superoxide dismutase, catalase, and glutathione peroxidase activities in intestinal and hepatic tissues. These were coupled with the suppression of I/R-induced bacterial translocation, downregulation of I/R-induced activation of Bax/caspase 3 signaling, and improvement of I/R-induced distortion of intestinal and hepatic histoarchitecture by Phyllanthus amarus. Conclusion: Methanolic Phyllanthus amarus leaf extract protects against intestinal and hepatic injuries associated with intestinal I/R by suppressing oxidative-stress-mediated activation of Bax/caspase 3 signaling. The beneficial effects of Phyllanthus amarus may be ascribed to its constituent bioactive molecules, especially tannins, anthocyanin, alkaloids, and phenolics.

Asunto(s)

Phyllanthus , Daño por Reperfusión , Animales , Antioxidantes , Caspasa 3 , Febuxostat , Isquemia , Masculino , Metanol , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , Reperfusión , Daño por Reperfusión/tratamiento farmacológico , Agua , Proteína X Asociada a bcl-2

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Irisin is a novel skeletal muscle- and adipose tissue-secreted peptide. It is conventionally regarded as an adipomyokine and is a cleaved fragment of Fibronectin type III domain-containing protein 5 (FNDC5). It is involved in the browning of white adipose tissue, glucose tolerance, and reversing of metabolic disruptions. Fertility is closely linked to energy metabolism and the endocrine function of the adipose tissue. Moreover, there is established association between obesity and male infertility. Irisin bears strong therapeutic promise in obesity and its associated disorders, as well as shown to improve male reproductive functions. Thus, irisin is a molecule of great interest in exploring the amelioration of metabolic syndrome or obesity-induced male infertility. In this review we aim to enumerate the most significant aspects of irisin actions and discuss its involvement in energy homeostasis and male reproduction. Though current and future research on irisin is very promiscuous, a number of clarifications are still needed to reveal its full potential as a significant medicinal target in several human diseases including male infertility.

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This study investigated the impact of the administration of HAART and anti-Koch's, singly and in combination, on sexual competence and birth statistics. Adult male Wistar rats were randomised into distilled water-treated control, HAART-treated, anti-Koch's-treated and HAART + anti-Koch's-treated groups. The 56-day oral treatment led to impaired sexual competence evident by significantly reduced motivation to mate, prolonged latencies of mount, intromissions, ejaculations and post-ejaculatory interval, as well as reduced frequencies of mount, intromissions and ejaculations. This was accompanied by significant reductions in penile erection reflex and penile grooming. HAART and anti-Koch's, when administered singly or in combination, also led to significant reductions in the circulatory follicle-stimulating hormone, luteinizing hormone, testosterone and intratesticular testosterone, but a significant rise in prolactin. Also, HAART and/or anti-Koch's significantly reduced sperm count, sperm motility, sperm viability and spermatozoa with normal morphology. Furthermore, HAART and anti-Koch's, separately or in combination, significantly lowered fertility capacity, litter size and litter weight and offspring survival. The deleterious effects of these drugs were more pronounced when combined. Findings of the present study revealed that HAART and/or anti-Koch's impair sexual competence via a testosterone-dependent hyperprolactinemia-mediated mechanism. These events are associated with reduced fertility capacity, poor sperm quality and lowered offspring survival.

Asunto(s)

Terapia Antirretroviral Altamente Activa , Motilidad Espermática , Adulto , Animales , Terapia Antirretroviral Altamente Activa/efectos adversos , Hormona Folículo Estimulante , Humanos , Hormona Luteinizante , Masculino , Ratas , Ratas Wistar , Recuento de Espermatozoides , Espermatozoides , Testosterona

RESUMEN

Sexual activity is an essential part of reproductive functions and needed for the maintenance of fertility. Drugs, particularly substances of abuse, impair male reproductive function either by interrupting hormonal functions or through the nonhormonal pathways. This study evaluated the impact of Rohypnol use in sexual behaviour. Materials and methods: Thirty adult male Wistar rats of comparable weights (180-200 g) were randomly allocated into three groups, the control and low-dose and high-dose Rohypnol-treated groups. The control group received 0.5 ml of distilled water, while the low- and high-dose Rohypnol-treated groups received 2 mg/kg b.w and 4 mg/kg b.w of Rohypnol via oral lavage once daily for 28 days. Rohypnol significantly increased mount latency, intromission latency, ejaculation latency and post-ejaculatory interval, as well as lowered mount frequency, intromission frequency and ejaculation frequency. Rohypnol-induced sexual dysfunction was found to be associated with significant suppression of circulatory follicle-stimulating hormone, luteinising hormone, testosterone and oestrogen. The present study reveals that Rohypnol induces sexual dysfunction through suppression of hypothalamic-pituitary-testicular axis. It also implicates Rohypnol as a potential candidate for drug-induced infertility.

Asunto(s)

Flunitrazepam , Conducta Sexual Animal , Animales , Eyaculación , Masculino , Extractos Vegetales , Ratas , Ratas Wistar , Testosterona

RESUMEN

Male factor accounts for about 30-50% of infertility. A common cause of male infertility is drug abuse; either illicit or prolonged use of prescribed drugs. This study provides a review of the physiology of the hypothalamic-pituitary-gonadal axis and recent literature on drugs that have been linked to male infertility and the associated mechanisms. Relevant peer-reviewed papers were assessed online using PubMed/PubMed Central, Scopus, AJOL, Google Scholar and DOAJ databases using Medical Subjects Headings (MeSH) indexes and relevant key word searches. Although drugs are beneficial when used at therapeutic levels, the abuse leads to impairment of hypothalamic-pituitary-gonadal functions, increased sperm DNA fragmentation and apoptosis, and reduced sperm quality. A good knowledge of the physiology of the hypothalamic-pituitary-gonadal axis and the influence of drugs on male fertility will guide healthcare providers in managing cases of infertility.

Asunto(s)

Infertilidad Masculina , Preparaciones Farmacéuticas , Fertilidad , Humanos , Infertilidad Masculina/inducido químicamente , Masculino , Reproducción , Espermatozoides

RESUMEN

ABSTRACTBackground: Opioids have been implicated to induce infertility. Although codeine remains the most used opioid for recreational purpose, no study has documented its effect on sperm quality. Elucidating the effect of codeine on sperm cells and the associated mechanisms may provide an insight into preventing drug-induced sperm damage. Twenty-one New Zealand white rabbits were randomized into three groups; control and codeine-treated. The codeine-treated groups received either 4 or 10mg/kg b.w of codeine for six weeks.Results: Codeine treatment led to significant decrease in sperm count, motility, viability, normal morphology, and sperm membrane integrity. This was associated with significant rise in sperm DNA fragmentation, oxidative damage, and caspase 3 activity. The percentage of sperm DNA fragmentation correlates positively with 8-hydroxy-2'-deoxyguanosine, a biomarker of oxidative DNA damage, and caspase 3 activity, a biomarker of apoptosis. The observed correlation was stronger between sperm DNA fragmentation and oxidative DNA damage than sperm DNA fragmentation and caspase 3 activity.Conclusion: This study revealed that chronic codeine exposure causes sperm DNA fragmentation and poor sperm quality primarily via oxidative stress rather than activation of caspase 3-dependent apoptosis. Findings of the present study may explain drug-induced male factor infertility, particularly, those associated with opioid use.

Asunto(s)

Apoptosis , Codeína/toxicidad , Daño del ADN , Infertilidad Masculina/patología , Estrés Oxidativo , Espermatozoides/patología , Animales , Infertilidad Masculina/etiología , Masculino , Narcóticos/toxicidad , Conejos , Espermatozoides/efectos de los fármacos