Bisphenol A (BPA) induces apoptosis of mouse Leydig cells via oxidative stress

Abstract

As one of the most frequently produced synthetic compounds worldwide, bisphenol A (BPA) has been widely used in many kinds of products such as appliances, housewares, and beverage cans. BPA has been shown to cause damage to male reproductive system; however, the potential mechanism remains to be investigated. In the present study, BPA exposure decreased the testis and epididymis coefficient, caused a disintegration of germinal epithelium, decreased the density and motility of sperm in the epididymis tissue, and increased the number of abnormal sperm morphology, which indicated that BPA exposure could cause damage to testis. BPA was also shown to induce apoptosis and oxidative stress in the testis tissue. The serum testosterone concentration was decreased in the BPA-treated group, suggesting that BPA could lead to Leydig cell damage. Subsequently, mouse TM3 cell, a kind of mouse Leydig cell line, was utilized to investigate the potential mechanism. Herein, we showed that BPA exposure could inhibit cell viability and induce apoptosis of TM3 cells. Furthermore, oxidative stress in the cells could also be induced by BPA, while the inhibition of oxidative stress by N-acetyl-L-cysteine (NAC), an oxidative stress scavenger, could reverse the inhibition of cell viability and induction of apoptosis by BPA exposure, indicating that oxidative stress was involved in BPA-induced apoptosis of TM3 cells. Finally, RNA-sequencing and real-time PCR were utilized to screen and validate the potential oxidative stress-related genes involving in BPA-induced apoptosis. We found that BPA exposure increased the mRNA levels of oxidative stress-related genes such as Lonp1, Klf4, Rack1, Egln1, Txn2, Msrb1, Atox1, Mtr, and Atp2a2, as well as decreased the mRNA level of Dhfr gene; while NAC could rescue the expression of these genes. Taken together, oxidative stress was involved in BPAinduced apoptosis of mouse Leydig cells.

Hepatoprotective effect of Artemisia Argyi essential oil on bisphenol A‐induced hepatotoxicity via inhibition of ferroptosis in mice

“…54,55 The evidences have demonstrated that inflammation was closely related with the XOD and disorders of PUFA. 56,57 Excitingly, AAEO could reverse the disturbance of purine metabolism by reducing the activity of XOD, and significantly reduce oxidative stress and the inflammatory responses in liver tissues by increasing the mRNA expressions of SOD and CAT in mice liver tissues.…”

“…Besides, XOD generated a large amount of ROS in the process of catalyzing hypoxanthine and xanthine to produce uric acid, which caused severe oxidative stress‐induced hepatotoxicity 54,55 . The evidences have demonstrated that inflammation was closely related with the XOD and disorders of PUFA 56,57 . Excitingly, AAEO could reverse the disturbance of purine metabolism by reducing the activity of XOD, and significantly reduce oxidative stress and the inflammatory responses in liver tissues by increasing the mRNA expressions of SOD and CAT in mice liver tissues.…”

Melatonin alleviates oxidative stress damage in mouse testes induced by bisphenol A

“…Leydig cells in mammalian testicular tissue can synthesize and secrete testosterone, and high levels of testosterone are necessary for normal spermatogenesis ( Chung et al, 2020 ). BPA reduces the expression of Leydig cell steroidogenic enzymes, including StAR, CYP11A1, CYP17A1, and 17β-HSD, thereby impacting testosterone synthesis and secretion ( Zhang et al, 2023 ). Cholesterol is the precursor for testosterone synthesis, and it is transported by StAR to the inner mitochondrial membrane ( Stocco, 2000 ).…”

Protective Effects of Selenium Nanoparticles against Bisphenol A-Induced Toxicity in Porcine Intestinal Epithelial Cells

“…It has been shown that BPA-treated rat and human stem cells have a significant decrease in cell viability and substantial apoptosis as early as 10 min of exposure and at physiologically relevant low doses [ 44 ]. At the same time, it was found that BPA induced apoptosis of mouse interstitial cells through oxidative stress [ 45 ]. Treatment with Se significantly alleviated Cd-induced apoptosis in chicken livers, as evidenced by a reduction in the production of NO, iNOS activity, the number of apoptotic cells, and mRNA and protein expression levels of caspase-3 and Bax [ 46 ].…”