Impaired expression of sex hormone receptors in male reproductive organs of diabetic rat in response to oral antidiabetic drugs

Ayuob, Nasra Naeim; Murad, Hussam; Ali, Soad Shaker

doi:10.5603/fhc.a2015.0005

Cited by 30 publications

(21 citation statements)

References 47 publications

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“…Serum testosterone levels also remained diminished in all the diabetic rats. Reduced serum testosterone in diabetic rats was attributed in previous studies to neuroendocrine dysfunction and the absence of the stimulatory effect of insulin on the Leydig cells [19,45].…”

Section: Discussionmentioning

confidence: 99%

“…BRCA 1 and 2 antibodies were diluted 1:100 and incubated on sections. These were followed by the biotinylated secondary antibody, streptavidin and DAB/ /substrate reaction according to Nasra [19].…”

Section: Methodsmentioning

confidence: 99%

“…Although not all diabetic men are infertile, evidences strongly associate T2DM with high prevalence of male subfertility/infertility [16] with associated reduction in birth rates [17]. Consequently, the disturbing increase in the number of diabetic men in reproductive age as well as the multiple molecular mechanisms and pathways that are affected by DM with substantial effects on male reproductive function [18,19].…”

Section: Introductionmentioning

confidence: 99%

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Impaired expression of testicular androgen receptor and collagen fibers in the testis of diabetic rats under HAART: the role of Hypoxis hemerocallidea

Ismail

Isaac

Offor

et al. 2017

Folia Histochem Cytobiol.

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introduction. Wide spectrum of alterations associated with highly active antiretroviral therapy (HAART) has been reported. The current study aimed at evaluating the role of Hypoxis hemerocallidea (HH) aqueous extract on the testosterone levels, expression of androgen receptors and collagen fibers in the testes of streptozotocin--nicotinamide-induced diabetic rats under HAART regimen. Material and methods. Sixty two adult male Sprague-Dawley rats (189.0 ± 4.5 g) were divided into eight groups (8 animals in each treatment groups and 6 rats in the control group). Diabetes was induced by a single intraperitoneal injection of nicotinamide (110 mg/kg bw) followed by streptozotocin (45 mg/kg bw) and the animals were then subjected to various treatments with HAART, HH extract or melatonin. At the end of the experiment, blood samples were collected to measure serum testosterone levels. Testes were fixed in buffered formaldehyde and paraffin processed. The expression of androgen receptor (AR) was assessed by immunohistochemistry and collagen fibers were visualized by Masson trichrome staining. results. Serum testosterone level was drastically (p < 0.0001) reduced in all rats with induced diabetes. In the testis of diabetic rats increased collagen fibers deposition with varying derangements in germinal epithelium of spermatogenic layers were observed. Intertubular hemorrhages and absence of spermatozoa were also noted in the testes of diabetic rats subjected to HAART. Reduced immunoexpression of ARs was found in the nuclei of Sertoli cells and the cytoplasm of spermatogonia and spermatocytes in III-IV stages of the seminiferous epithelium cycle of diabetic animals treated with different dosages of HH alone and those treated with HAART concomitantly with melatonin and HH. The expression of ARs was almost negative in the testes of rats treated with HAART alone. Conclusions. Concomitant treatment of rats with aqueous HH extract during the HAART did not change serum testosterone level nor mitigate the altered expression of collagen fibers and androgen receptor resulting from STZ-nicotinamide-induced diabetes. Therefore, anti-diabetic properties of Hypoxis extract require further investigation.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Impaired expression of testicular androgen receptor and collagen fibers in the testis of diabetic rats under HAART: the role of Hypoxis hemerocallidea

Ismail

Isaac

Offor

et al. 2017

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

show abstract

“…The rats were randomly divided into three groups (n=6 per group). Rats in the control group received a standard diet, while the HFD group received an HFD, and the metformin group received an HFD plus metformin (Sigma-Aldrich) treatment (100 mg/kg, once daily by oral gavage) [13]; the control and HFD groups received saline simultaneously. The full compositions of the standard and HFDs have been reported previously [14].…”

Section: Animal Experimentsmentioning

confidence: 99%

Protective effects of metformin on reproductive function in obese male rats induced by high-fat diet

Yan

et al. 2015

J Assist Reprod Genet

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Purpose The study aims to elucidate the changes in testicular spermatogenic function in high-fat diet (HFD)-induced obese rats and to evaluate the protective effects of metformin intervention. Methods Male Sprague-Dawley rats (n=18) were randomly divided into a control group (standard diet), an HFD group, and a metformin group (HFD + metformin at 100 mg/kg, once daily by oral gavage). After 8 weeks, rats were euthanized, and the weights of body and testes were measured. Testis and epididymis were dissected and hematoxylin-eosin-stained for histopathological examination and semen parameter analysis. Blood samples were collected for assessment of sex hormones and metabolic parameters (serum glucose, insulin, and leptin). Spermatogenic cell apoptosis was accessed by TUNEL. Results Compared with the control group, the final body weight and weight gain were significantly higher in HFD rats, while the testicle weight and coefficients were lower. In HFD rats, metformin treatment induced weight loss and increased testicle weight (P<0.05). In HFD rats, obvious pathological changes in the testicular tissue were characterized by small, atrophic, and distorted seminiferous tubules and destroyed basement membrane. Metformin treatment protected against the HFD-induced decrease in the number of spermatogonia, Sertoli cells, and Leydig cells (P<0.05); ameliorated the HFD-induced increases in serum glucose, insulin, leptin, and estrogen; and decreased serum testosterone (P<0.05) and reduced the rate of testicular cell apoptosis in obese male rats. Finally, metformin significantly improved semen parameters (including concentration, viability, motility, and normal morphology) in HFD rats (P<0.05). Conclusions HFD-induced obesity in rats results in detrimental effects on spermatogenesis, semen quality, endogenous hormones, and testicular cell apoptosis. Metformin intervention improved the semen parameters, possibly due to its effects on weight loss, increased testicular weight, reduced testicular cell apoptosis, and resulted in restoration of hormonal homeostasis and correction of metabolic disorder.

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“…The study conducted by Adaramoye and Lawal (2014) on diabetic male rats showed that metformin is able to restore follicle-stimulating hormone, leutinizing hormone, and testosterone (Adaramoye, Lawal, 2014). Likewise, oral administration of metformin succeeded to restore testosterone level back to normal in diabetic rats (Ayuob, Murad, Ali, 2015). …”

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confidence: 99%

Effect of metformin on semen quality

Banihani

2016

Braz. J. Pharm. Sci.

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Various studies have linked metformin, a universally antidiabetic drug, with semen quality; however, such a direct link has not been established. This review systematically addresses and summarizes the effect of metformin on semen quality, particularly sperm function. We searched the MEDLINE electronic database for English articles and abstracts containing the key words 'metformin' and 'sperm', and relevant articles were reviewed. In summary, metformin appears to have improved and provided positive impact on sperm quality. This effect may be due to the ability of metformin to reduce oxidative stress and lipid peroxidation, enhance 5'-AMP activated protein kinase activity, and restore the normal levels of pituitary-gonadal hormones. However, further clinical research is still necessary to confirm such effect.Uniterms: Metformin/effects. Metformin/review. Metformin/semen quality. Sperm/study. Testosterone. Oxidative stress. 5'-AMP activated protein kinase. INTRODUCTIONMetformin, a biguanide-derivative antidiabetic drug, is the most widely used oral agent in humans (Brinkmann, Brixius, 2015;Chhetri, Thapa, Van Schepdael, 2014). It is the first-line drug for the treatment of type 2 diabetes, particularly, in overweight and obese patients with normal kidney function (American Diabetes, 2009;George, Joseph, 2014;Hung et al., 2015). In addition, recent research has proposed that metformin alone or in combination with insulin may be safe to treat gestational diabetes and does not increase the risk of metabolic acidosis (Huang, Castelino, Peterson, 2015; Kitwitee et al., 2015). Metformin's mechanism of action involves suppression of hepatic gluconeogenesis (Ferrannini, 2014; Foretz et al., 2010;Todd, Florez, 2014). One concern that has been raised relevant to metformin usage is that the consensus panel of diabetes felt that metformin should be considered for diabetes prevention even in non-diabetic individuals (i.e., pre-diabetic or obese individuals). This concern increases the use of this drug by these groups (American Diabetes, 2009;Hostalek, Gwilt, Hildemann, 2015;Manu et al., 2015;McGavock, Dart, Wicklow, 2015).Over the last decade, various experimental and clinical studies have linked metformin with sperm function, and thus with male factor infertility Ferreira et al., 2015); however, such direct link has not been established. In this review, we provide fresh and comprehensive understanding of the effect of metformin, as a universally used oral agent, on semen quality (i.e., sperm quantity and quality). To do this, we searched the MEDLINE electronic database for English-language articles and abstracts reported using the key words 'metformin' and 'sperm'. The references from selected articles were reviewed and used if relevant. Effect of metformin on sperm parameters Positive effectsTo date, the majority of studies linking metformin to sperm parameters are nonclinical. In his study on streptozotocin-induced diabetic rats, Attia, Helal, Alhaider (2009) made the seminal observation that metformin decreases the diabe...

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Impaired expression of sex hormone receptors in male reproductive organs of diabetic rat in response to oral antidiabetic drugs

Cited by 30 publications

References 47 publications

Impaired expression of testicular androgen receptor and collagen fibers in the testis of diabetic rats under HAART: the role of Hypoxis hemerocallidea

Impaired expression of testicular androgen receptor and collagen fibers in the testis of diabetic rats under HAART: the role of Hypoxis hemerocallidea

Protective effects of metformin on reproductive function in obese male rats induced by high-fat diet

Effect of metformin on semen quality

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