Endoplasmic reticulum stress and mitochondrial injury are critical molecular drivers of AlCl3-induced testicular and epididymal distortion and dysfunction: protective role of taurine

Abstract

Aluminum, the third most plentiful metal in the Earth’s crust, has potential for human exposure and harm. Oxidative stress plays an essential role in producing male infertility by inducing defects in sperm functions. We aimed to investigate the role of endoplasmic reticulum (ER) stress and mitochondrial injury in the pathogenesis of aluminum chloride (AlCl3)-induced testicular and epididymal damage at the histological, biochemical, and molecular levels, and to assess the potential protective role of taurine. Forty-eight adult male albino rats were separated into four groups (12 in each): negative control, positive control, AlCl3, and AlCl3 plus taurine groups. Testes and epididymis were dissected. Histological and immunohistochemical (Bax and vimentin) studies were carried out. Gene expression of vimentin, PCNA, CHOP, Bcl-2, Bax, and XBP1 were investigated via quantitative real-time polymerase chain reaction (qRT-PCR), besides estimation of malondialdehyde (MDA) and total antioxidant capacity (TAC). Light and electron microscopic examinations of the testes and epididymis revealed pathological changes emphasizing both mitochondrial injury and ER stress in the AlCl3 group. Taurine-treated rats showed a noticeable improvement in the testicular and epididymal ultrastructure. Moreover, they exhibited increased gene expression of vimentin, Bcl-2, and PNCA accompanied by decreased CHOP, Bax, and XBP1 gene expression. In conclusion, male reproductive impairment is a significant hazard associated with AlCl3 exposure. Both ER stress and mitochondrial impairment are critical mechanisms of the deterioration in the testes and epididymis induced by AlCl3, but taurine can amend this.

Effects of thymoquinone against D- galactose and aluminum chloride induced testicular dysfunction in rats.

“…MDA is an important oxidant parameter for testicles [47]. In previous studies, it has been stated that AlCl3 weakens the antioxidant system in rats by increasing the MDA content [48,49]. It is stated that D-Gal induces oxidative stress by increasing lipid peroxidation [11].…”

Smart Hesperidin/Chitosan Nanogel Mitigates Apoptosis and Endoplasmic Reticulum Stress in Fluoride and Aluminum-Induced Testicular Injury

“…In our study PERK, ATF 6, and IRE 1-α gene expression were significantly upregulated in the AlCl 3 + NaF intoxicated group, indicative of ER stress. Two different studies on fluoride [ 116 , 117 ] and aluminum [ 118 ] suggested that ER-mediated apoptosis is a critical mechanism for their testicular toxicity. It has been reported that HSP can ameliorate ER stress in fluoride [ 30 ], abamectin [ 119 ], and paclitaxel [ 113 ]-induced testicular toxicity.…”

Exogenous taurine administration abates reproductive dysfunction in male rats exposed to silver nanoparticles

“…Taurine is well‐acknowledged to possess anti‐inflammatory, antioxidant, anti‐peroxidative, and anti‐apoptotic activities in animals and humans 31,32 . Previous experimental data demonstrated that taurine mitigated reproductive toxicity induced by aluminum in rats, 33 lead acetate in mice 34 as well as reproductive dysfunction in diabetic and hypertensive rats 35,36 …”