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Testosterone recuperates deteriorated male fertility in cypermethrin intoxicated rats.

ABSTRACT: The present study investigates the protective effects of testosterone against reproductive toxicity induced by cypermethrin (50 mg/kg body weight) in rats. Significant reduction in the testicular and accessory sex organ weights were observed in cypermethrin-treated rats over controls. Cypermethrin intoxication significantly reduced testicular daily sperm count, epididymal sperm count, sperm motility, sperm viability and HOS-tail coiled sperm accompanied by significant reduction in the activity levels of testicular steroidogenic enzymes such as 3β- and 17β- hydroxysteroid dehydrogenases in rats as compared to controls. Further, qPCR studies indicated that the mRNA expression levels of steroidogenic acute regulatory protein (StAR) significantly decreased in cypermethrin-treated rats over controls. Molecular docking analysis indicated that the binding affinity of cypermethrin (- 11.2 kcal/mol) towards StAR protein was greater as compared to its natural ligand, cholesterol (- 8.2 kcal/mol) suggesting improper cholesterol channeling across the testis. Significant reduction in the circulatory levels of testosterone was also recorded in cypermethrin-exposed rats. An increase in pre- and post-implantation loss was observed in rats cohabited with cypermethrin-treated rats. On the other hand, testosterone (4.16 mg/kg body weight) treatment ameliorated cypermethrin-induced reprotoxic effects in rats. To conclude, cypermethrin-induced deterioration of suppressed reproductive performance in male rats could be linked to its antiandrogenic effects and on the other hand, testosterone-mediated protection of male reproductive health in cypermethrin-treated rats at least in part occurs via restoration of testosterone biosynthesis, spermatogenesis and sperm maturation events.

SUBMITTER: Katragadda V

PROVIDER: S-EPMC7806673 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Leydig cells secrete the steroid hormone, testosterone, which is essential for male fertility and reproductive health. Stress increases the secretion of glucocorticoid [corticosterone, (CORT) in rats] that decreases circulating testosterone levels in part through a direct action on its receptors in Leydig cells. Intratesticular CORT level is dependent on oxidative inactivation of CORT by 11?-hydroxysteroid dehydrogenase 1 (HSD11B1) in rat Leydig cells. Pain may cause the stress, thus affecting testosterone production in Leydig cells. Methods: Adult male Sprague-Dawley rats orally received vehicle control or 5 or 10 mg/kg dehydroepiandrosterone (DHEA) 0.5 h before being subjected to pain stimulation for 1, 3, and 6 h. In the present study, we investigated the time-course changes of steroidogenic gene expression levels after acute pain-induced stress in rats and the possible mechanism of DHEA that prevented it. Plasma CORT, luteinizing hormone (LH), and testosterone (T) levels were measured, and Leydig cell gene expression levels were determined. The direct regulation of HSD11B1 catalytic direction by DHEA was detected in purified rat Leydig, liver, and rat Hsd11b1-transfected COS1 cells. Results: Plasma CORT levels were significantly increased at hour 1, 3, and 6 during the pain stimulation, while plasma T levels were significantly decreased starting at hour 3 and 6. Pain-induced stress also decreased Star, Hsd3b1, and Cyp17a1 expression levels at hour 3. When 5 and 10 mg/kg DHEA were orally administered to rats 0.5 h before starting pain stimulation, DHEA prevented pain-mediated decrease in plasma T levels and the expression of Star, Hsd3b1, and Cyp17a1 without affecting plasma CORT levels. DHEA was found to modulate HSD11B1 activities by increasing its oxidative activity and decreasing its reductive activity, thus decreasing the intracellular CORT levels in Leydig cells. Conclusion: Stress induced by acute pain can inhibit Leydig cell T production by upregulation of corticosterone. DHEA can prevent the negative effects of excessive corticosterone by modulating HSD11B1 activity.

Project description:Cypermethrin (CYP) is a synthetic pyrethroid utilized as an insecticide in agriculture and various pest eradication programs. However, it induces numerous health hazards for animals and humans. Therefore, the current study used Panax ginseng root extract (ginseng) to reduce the hepatorenal damage caused by commercially used CYP. Thirty-two male Wistar albino rats were distributed into control, ginseng (300 mg/kg B.W/day), CYP (4.67 mg/kg B.W.), and Ginseng+CYP (rats received both CYP and ginseng). All treatments were administered orally for 30 consecutive days. Cypermethrin induced harmful effects on hepatic and renal tissues through a substantial decline in body weight in addition to a considerable increase in liver enzymes, functional renal markers, and cholesterol. Also, CYP significantly decreased acetylcholinesterase (AChE) activity and increased pro-inflammatory cytokines (interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α)). Moreover, a marked increase in malondialdehyde level with a significant drop in reduced glutathione level and total superoxide dismutase (T-SOD) and catalase (CAT) activities was reported in the CYP group in kidney and liver tissues. Additionally, CYP exhibited affinities to bind and inhibit AChE and antioxidant enzymes (T-SOD and CAT) in rats following the molecular docking modeling. The apparent hepatorenal oxidative damage was linked with obvious impairments in the liver and kidney histoarchitecture, immunohistochemical staining of B cell lymphoma-2 (Bcl-2), and caspase-3 proteins. Ginseng reduced CYP's oxidative alterations by repairing the metabolic functional markers, improving antioxidant status, reducing the inflammatory response, and enhancing the molecular docking evaluation. It also ameliorated the intensity of the histopathological alterations and improved the immunohistochemical staining of Bcl-2 and caspase-3 proteins in the liver and kidney tissues. Finally, concomitant oral administration of ginseng mitigated CYP-prompted hepatorenal damage through its antioxidant, anti-inflammatory, and anti-apoptotic potentials.

Project description:AimThe aim of this study was to evaluate the relationship of scrotal circumference (SC) with plasma testosterone, seminal vesicles (SVs) weight, and its secretion as measurable indicators of fertility and also to sequence and establish phylogenetic relatedness of certain SV protein genes with other species as such integrated approach is lacking.Materials and methodsAltogether, 59 apparently healthy male buffaloes sacrificed at slaughterhouse were selected (irrespective of breed) for measuring SC and collecting blood and paired SVs. The SC was measured at greater curvature using soft thread. In the present study, blood plasma testosterone, cholesterol, protein, and glucose in addition to SV fructose, citric acid and proteins in SV fluid were also estimated. The SV tissue was fixed in RNAlater for RNA extraction. Male buffaloes were categorized as per total SV weight into Group I (<5.0 g), Group II (5.0-7.84 g), and Group III (>8.0 g) and dentitions-I (≤18 months), II (18-24 months), and III (≥24 months) to assess the effect of weight and dentition age on SC, SV weight, and its certain secretions. Data were analyzed using linear model procedure including Tukey HSD test and Pearson's correlation coefficient. Variance inflation and condition index were also used to assess multicollinearity.ResultsGross and histomorphological evaluation of SVs did not show any abnormality. Macronutrients (plasma protein, glucose, and cholesterol) showed non-significant (p>0.05) variation between groups. The SC and SV weight varied significantly (p<0.05) with a significant positive relationship with plasma testosterone, SV protein, fructose, and citric acid. In addition, testosterone concentration also showed increasing trend from Groups I to III but increased significantly (p<0.05) from Group II to III with positive and significant correlations with SV protein, fructose, and citric acid similar to SV weight and SC. Binders of sperm protein (BSP1, 3, and 5) genes (full length) were sequenced and established an evolutionary relationship which is lacking in buffalo.ConclusionThe present findings established a significant positive correlation of SC with that of other fertility parameters related to SVs weight and its secretions: Fructose, citric acid, and protein (inclusive of BSPs sequenced full length), and testosterone. Therefore, the present integrated approach along with certain semen quality attributes reflecting epididymis function could be used as a predictive fertility marker for grading and selection of breeding bulls and their progenies to develop outstanding bull mother farm.

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Testosterone recuperates deteriorated male fertility in cypermethrin intoxicated rats.

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