Methotrexate Changes the Testicular Tyrosine Phosphorylated Protein Expression and Seminal Vesicle Epithelia of Adult Rats

Abstract

IAMSAARD, S.; WELBAT, J. U.; SUKHORUM, W.; KRUTSRI, S.; ARUN, S. & SAWATPANICH, T. Methotrexate changes the testicular tyrosine phosphorylated protein expression and seminal vesicle epithelia of adult rats. Int. J. Morphol., 36(2):737-742, 2018. SUMMARY: Methotrexate (MTX) is commonly used as a chemotherapy agent and immune system suppressant but its adverse effect on male reproductive system is still limited. This study aimed to investigate the effect of MTX on structure and functional proteins of testis and seminal vesicle. Adult male rats were divided into control and MTX groups (n =12). In 30 experimental days, the treated animals were injected with MTX (tail i.v., 75 mg/KgBW) at days 8 and 15. Then, the reproductive parameters and histology of both groups were examined. Thickness of seminal seminal vesicle epithelia was analyzed. Also, the expressions of testicular tyrosine phosphorylated proteins and steroidogenic acute regulatory (StAR) protein were investigated. The results showed that MTX could significantly decrease epididymal sperm concentration. In addition, the germ cell degeneration, increased spaces of interstitial tissues, and low epididymal sperm mass density were observed in MTX group. The thickness of seminal vesicle epithelia in MTX group was significantly lower than that of control group. Moreover, the intensity of testicular phosphorylated proteins of 31, 32, 72, and 85 kDas was significantly increased while of 42 and 47 kDas in MTX group was decreased as compared to control. The expression of testicular StAR protein in MTX group was also significantly decreased as compared to the control. In conclusion, MTX affects testicular and seminal tissues and changes testicular functional proteins in adult rats. KEY WORDS: Methotrexate; Phosphorylated proteins; Testis; Seminal vesicle; Male rat. IAMSAARD, S.; WELBAT, J. U.; SUKHORUM, W.; KRUTSRI, S.; ARUN, S. & SAWATPANICH, T. El metotrexato cambia la expresión de la proteína testicular-tirosina fosforilada y el epitelio vesicular seminal en ratas adultas. Int. J. Morphol., 36(2):737-742, 2018.

Valproic acid changes the expression of tyrosine‐phosphorylated proteins in rat seminal vesicle

“…Changes in TyrPho protein expression in the testis have been associated with stress‐related and diabetic conditions (Arun, Burawat, Sukhorum, Sampannang, Maneenin, et al, ; Arun, Burawat, Sukhorum, Sampannang, Uabundit, et al, ; Sampannang, Arun, Burawat, Sukhorum, & Iamsaard, ; Sampannang et al, ). Moreover, some anticancer drugs, such as VPA, methotrexate, ketoconazole and mimosine, have been shown to alter the patterns of TyrPho proteins in the testis and epididymis (Burawat et al, ; Iamsaard et al, , , ; Maneenin et al, ; Sawatpanich et al, ; Sukhorum & Iamsaard, ). Although the toxic effects of VPA on some male reproductive organs (especially the testis and epididymis) have been demonstrated, its effect on the seminal vesicle, the biggest accessory organ that produces essential seminal plasma nutrients, has never been reported.…”

Phyllanthus emblica leaf extract ameliorates testicular damage in rats with chronic stress

“…This indicates that those proteins are involved in normal testicular function such as sperm and testosterone production. Moreover, various studies have demonstrated that changes in testicular tyrosine phosphorylation can occur with exposure to drugs, toxic substances, or herbal preventive treatments, especially those that use plant extracts in traditional medicine (Arun et al, 2016a(Arun et al, , 2016bSampannang et al, 2017;Sukhorum and Iamsaard, 2017;Iamsaard et al, 2018;Maneenin et al, 2018).…”

Effect of ethanol on the changes in testicular protein expression in adult male rats

“…Many studies have reported that expressions of testicular TyrPho proteins are altered in infertile conditions associated with decrease in testosterone level (Arun, Burawat, Sukhorum, Sampannang, Maneenin, et al, 2016; Arun, Burawat, Sukhorum, Sampannang, Uabundit, et al, 2016; Burawat et al., 2018; Chaichun et al., 2019; Iamsaard et al., 2014, 2018; Sampannang et al., 2019; Sukhorum & Iamsaard, 2017). We assumed that the overexpression of testicular TyrPho proteins may associate with decreased testosterone level or involved in early apoptotic process in seminiferous epithelium of ethanol‐treated animals.…”

“…Interestingly, many tyrosine-phosphorylated (TyrPho) proteins have been localised and identified in testis, epididymis and seminal vesicle of rats (Chaichun, Arun, Burawat, Kanla, & Iamsaard, 2017;Sawatpanich et al, 2018;Tongpan, Sukhorum, Arun, Sawatphanich, & Iamsaard, 2019). Indeed, the alteration of TyrPho proteins is associated with male infertile conditions such as animals induced with anti-cancer drugs (Burawat, Uabandit, Arun, Nualkaew, & Iamsaard, 2018;Chaichun et al, 2019;Iamsaard et al, 2014Iamsaard et al, , 2018Sukhorum & Iamsaard, 2017;Tongpan et al, 2019), type 1 and 2 diabetes (Sampannang, Arun, Burawat, Sukhorum, & Iamsaard, 2019;Yannasithinon & Iamsaard, 2019), and acute and chronic stresses (Arun, Burawat, Sukhorum, Sampannang, Maneenin, et al, 2016;Arun, Burawat, Sukhorum, Sampannang, Uabundit, et al, 2016). However, the changes in testicular TyrPho proteins and other markers in sexually mature rats administered with ethanol have never been reported.…”