Comparison of male reproductive parameters in mice with type 1 and type 2 diabetes / 대한생식의학회지

Objective@#The differences between type 1 and type 2 diabetes mellitus (T1DM and T2DM) in terms of their adverse effects on male reproductive parameters have never been elucidated. This study aimed to distinguish between the effects of the DM types in mice treated with multiple low doses of streptozotocin (STZ) to mimic human T1DM and coadministered a high-fat diet (HFD) to mimic human T2DM. @*Methods@#The T1DM mice were intraperitoneally injected with STZ (40 mg/kg body weight) for 5 days. The T2DM mice received an HFD for 14 days prior to STZ injection (85 mg/kg body weight), followed by continuous feeding of an HFD. Male reproductive parameters were evaluated. @*Results@#The reproductive organs of the DM mice weighed significantly less than those of controls, and the seminal vesicles plus prostates of the T1DM mice weighed less than those of the T2DM mice. Increased sperm abnormalities and incomplete DNA packaging were observed in the DM groups. Sperm concentration and the proportion of normal sperm were significantly lower in the T1DM group. The seminiferous histopathology of DM mice was classified into seven types. The penises of the DM mice were smaller than those of the controls; however, tunica albuginea thickness and the amount of penile collagen fibers were increased in these mice. Round germ cells were abundant in the epididymal lumens of the mice with DM. @*Conclusion@#T1DM adversely affected reproductive parameters to a greater extent than T2DM.

Evaluation of antioxidant capacity and reproductive toxicity of aqueous extract of Thai Mucuna pruriens seeds / 中西医结合学报

OBJECTIVE@#In traditional medicine, the seeds of Thai Mucuna pruriens (T-MP) are used to treat male dysuria and are believed to enhance fertility. However, information pertaining to the toxicity of T-MP and its interaction with other properties is limited. This study was thus conducted to evaluate the antioxidant capacity and subacute toxicity of T-MP in the reproductive system.@*METHODS@#Total phenolic content and antioxidant capacity of T-MP seed extract were determined using total phenolic content, 2,2-diphenyl-1-picrylhydrazyl and ferric reducing antioxidant power assays. Male and female adult rats were treated orally with T-MP at a dosage of 150 or 300 mg/kg body weight for 14 consecutive days. Sex hormones and functional parameters in the liver and kidney were evaluated. Histopathology of all tissue was conducted using Masson's trichrome staining. Sperm parameters, including concentration, morphology, acrosome reaction status and DNA damage, were also examined. Expression of tyrosine phosphorylated protein (TyrPho), androgen receptor and A-kinase-anchoring protein 4 (AKAP4) were investigated using the Western blot technique.@*RESULTS@#T-MP seed extract contained phenolic compounds and exhibited high antioxidant capacity with no toxicity at the tested doses. It did not affect liver or kidney function parameters in the male rats, but increased estradiol, aspartate aminotransferase and alanine aminotransferase levels in the females. Additionally, it decreased serum progesterone and alkaline phosphatase levels in female rats. Serum and intratesticular testosterone levels were significantly lower in male rats that received a high dosage of T-MP. Histopathological changes were not observed in any tissue treated with T-MP. T-MP also significantly increased sperm concentration (but did not affect sperm parameters), and enhanced testicular TyrPho protein and androgen receptor and expression of AKAP4 in sperms.@*CONCLUSION@#T-MP seed extract exhibited antioxidant capacity and was not harmful to reproductive tissues. It also had a phytoestrogenic effect on females and increased the expression of testicular and sperm markers of male fertility.

Testicular histopathology and phosphorylated protein changes in mice with diabetes induced by multiple-low doses of streptozotocin: an experimental study

Background: The streptozotocin [STZ]-induced diabetic model is widely used to evaluate the adverse effects of diabetes mellitus [DM] on spermatogenesis and testicular steroidogenesis. However, the actual mechanism of sub/infertility in DM males needs to be elucidated

Objective: To conduct a detailed examination of the testicular histopathology, sperm acrosome reaction [AR] status, and tyrosine-phosphorylated protein expression in the testis of male mice induced with STZ

Materials and Methods: Ten ICR mice were divided into two groups [n=5/each]: control and diabetes induced by multiple low doses of streptozotocin [MLD-STZ]. The control mice were intraperitoneally injected with citrate buffer, whereas MLD-STZ mice were injected with STZ at 40 mg/kg body weight for five consecutive days. At the end of the experiment [day 40], reproductive parameters, AR status, and the histopathology of the testis and epididymis were evaluated. The expression of testicular tyrosine phosphorylated proteins was examined

Results: Blood glucose levels, AR percentages, and sperm abnormality of STZ group were significantly higher [p=0.003, 0.001, 0.000], while sperm concentration was significantly lower [p=0.001] compared to control. Histopathology of the seminiferous tubule was classified into 7 types. Additionally, abundant round cells were found in the epididymal lumen of the MLD-STZ mice. Moreover, the intensities of testicular phosphorylated proteins [170, 70, 36, 30, and 25 kDas] were markedly higher and a 120 kDa protein band was noticeably lower in the MLD-STZ mice

Conclusion: MLD-STZ-induced DM causes many testicular histopathologies, precocious sperm AR, and increased expression of testicular phosphorylated proteins. These findings may clarify some mechanisms of sub/infertility in DM males

Protective effect of Momordica cochinchinensis (L. ) spreng aril extract on essential testicular markers in rats induced with valproic acid / Efecto protector de Momordica cochinchinensis (L. ) extracto de aril en marcadores testiculares esenciales en ratas inducidas con ácido valproico

Valproic acid (VPA), an anti-epileptic drug, has been reported to cause male sub/infertility. Together with searching for alternative treatments, the degrees to which testosterone levels and sperm quality are decreased under VPA treatment also need to be clarified. This study aimed to investigate the protective effects of Momordica cochinchinensis (MC) aril extract containing antioxidant capacity on adverse reproductive parameters induced with VPA. Rats were divided into 6 groups (control, VPA, 200 mg kg-1 of MC only, 50, 100, 200 mg kg-1 MC+VPA, respectively, n=8 in each). Animals were pretreated with MC extract for 23 days before co-administration with VPA (500 mg kg-1, i.p.) for 10 consecutive days. All reproductive parameters including histology, and expression of androgen receptor (AR), Ki-67, tyrosine phosphorylated proteins, and steroidogenic proteins in testis were examined. The results showed that MC could prevent all reproductive parameters in VPA-treated rats. Moreover, MC+VPA groups showed significant declining of testicular histopathologies compared to VPA group. It also decreased the malondialdehyde level and changes of the testicular StAR, AR, and tyrosine phosphorylated protein expressions. In conclusion, M. cochinchinensis aril extract can prevent adverse male reproductive parameters and essential testicular proteins damages induced with VPA.

Se ha informado que el ácido valproico (VPA), un fármaco antiepiléptico, causa infertilidad masculina. Junto con la búsqueda de tratamientos alternativos, los grados a los que los niveles de testosterona y la calidad del esperma son disminuidos bajo el tratamiento de VPA también necesitan ser aclarados. El objetivo de este estudio fue investigar los efectos protectores del extracto aril de Momordica cochinchinensis (MC) que contiene capacidad antioxidante sobre parámetros reproductivos adversos inducidos con VPA. Las ratas se dividieron en 6 grupos (control, VPA, 200 mg kg-1 de MC solamente, 50, 100, 200 mg kg-1 de MC + VPA, respectivamente; n = 8 en cada uno). Los animales fueron pretratados con extracto de MC durante 23 días antes de la coadministración con VPA (500 mg kg-1, i.p.) durante 10 días consecutivos. Se examinaron todos los parámetros reproductivos, incluyendo la histología, y la expresión de receptor de andrógenos (AR), Ki-67, proteínas fosforiladas con tirosina y proteínas esteroidogénicas en los testículos. Los resultados mostraron que MC podría prevenir todos los parámetros reproductivos en las ratas tratadas con VPA. Además, los grupos MC + VPA mostraron una disminución significativa de las histopatologías testiculares en comparación con el grupo VPA. También disminuyó el nivel de malondialdehído y los cambios de las expresiones testiculares de las proteínas StAR, AR y tirosina fosforiladas. En conclusión, el extracto de aril de M. cochinchinensis puede prevenir los parámetros reproductivos masculinos adversos y los daños esenciales de proteínas testiculares inducidos con VPA.

Valproic acid induces histologic changes and decreases androgen receptor levels of testis and epididymis in rats

Background: valproic acid [VPA], an anti-epileptic drug, can cause male subfertility. However, the degree to which testicular and epididymal histopathologies and androgen receptor [AR] expression are changed under VPA treatment has never been reported

Objective: to investigate the histopathological changes and AR protein levels of testis and epididymis in VPA-treated rats for every single day

Materials and Methods: sixty-four adult male Wistar rats were divided into control and VPA-treated groups [n=8/ each]. Treated rats were injected with 500 mg/ kgBW, intraperitoneally, VPA for 10 consecutive days. At the end of every experimental day, all reproductive parameters including histology by hematoxylin and eosin staining and protein expression of AR by Immuno-Western blot in testis and epididymis were examined

Results: VPA-treated rats showed dramatically changes in testicular and epididymal histopathologies compared to control group. The multinucleated giant cells and sloughing of germ cells were observed on day 6. The germ cell disintegration and increased intercellular spaces of seminiferous tubular epithelium appeared in days 7-10 of VPA treatment. Additionally, extensive multinucleated giant cells and complete exfoliation were clearly found from days 8-10. Such exfoliated germ cells were clearly seen in its epididymal lumen at day 10. The increasing rate of sperm concentration was approximately 32.31% of that in control group at day 10 [p=0.03]. Moreover, the protein expressions of testicular and epididymal AR [% intensity/ 80 ?g protein lysate] was decreased in VPA-treated rats compared with control

Conclusion: VPA treatment induces histologic changes of germ cell epithelium in seminiferous tubules and decreases the expression of testicular and epididymal androgen receptors

Chronic restraint stress induces sperm acrosome reaction and changes in testicular tyrosine phosphorylated proteins in rats

Background: Stress is a cause of male infertility. Although sex hormones and sperm quality have been shown to be low in stress, sperm physiology and testicular functional proteins, such as phosphotyrosine proteins, have not been documented

Objective: To investigate the acrosome status and alterations of testicular proteins involved in spermatogenesis and testosterone synthesis in chronic stress in rats

Materials and Methods: In this experimental study, male rats were divided into 2 groups [control and chronic stress [CS], n=7]. CS rats were immobilized [4 hr/day] for 42 consecutive days. The blood glucose level [BGL], corticosterone, testosterone, acrosome status, and histopathology were examined. The expressions of testicular steroidogenic acute regulatory [StAR], cytochrome P450 side chain cleavage [CYP11A1], and phosphorylated proteins were analyzed

Results: Results showed that BGL [71.25 +/- 2.22 vs. 95.60 +/- 3.36 mg/dl], corticosterone level [24.33 +/- 4.23 vs. 36.9 +/- 2.01 ng/ml], acrosome reacted sperm [3.25 +/- 1.55 vs. 17.71 +/- 5.03%], and sperm head abnormality [3.29 +/- 0.71 vs. 6.21 +/- 1.18%] were significantly higher in CS group in comparison with control. In contrast, seminal vesicle [0.41 +/- 0.05 vs. 0.24 +/- 0.07 g/100g], testosterone level [3.37 +/- 0.79 vs. 0.61 +/- 0.29 ng/ml], and sperm concentration [115.33 +/- 7.70 vs. 79.13 +/- 3.65×106 cells/ml] of CS were significantly lower [p<0.05] than controls. Some atrophic seminiferous tubules and low sperm mass were apparent in CS rats. The expression of CYP11A1 except StAR protein was markedly decreased in CS rats. In contrast, a 55 kDa phosphorylated protein was higher in CS testes

Conclusion: CS decreased the expression of CYP11A, resulting in decreased testosterone, and increased acrosome-reacted sperm, assumed to be the result of an increase of 55 kDa phosphorylated protein