Melatonin Alleviates BPA-Induced Testicular Apoptosis and Endoplasmic Reticulum Stress.

Abstract

The impact of melatonin on bisphenol A (BPA)-induced testicular apoptosis and endoplasmic reticulum (ER) stress was explored. The mice received BPA (50 mg/kg) by gavage for 30 days while being injected with 20 mg/kg melatonin. Protein expressions were detected with western blotting. The Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) assay measured testicular cell apoptosis. Testosterone was quantified by employing enzyme-linked immunosorbent assay (ELISA). Melatonin promoted the development of seminiferous tubules, restored the orderly arrangement of the germ cells, and increased epithelial layers in the seminiferous tubules in BPA-treated mice. Moreover, in BPA-treated mouse testicular cells, melatonin markedly upregulated melatonin receptor 1A (MTNR1A) and melatonin Receptor 2 (MTNR2) expressions while downregulating ER molecular chaperones glucose-regulated protein 78 (GRP78) and glucose-regulated protein 94 (GRP94). Furthermore, it decreased p-PERK, p-IRE1, and ATF6α, as well as the apoptotic proteins cysteine-containing aspartate-specific proteases-12 (caspase-12) and cleaved cysteine-containing aspartate-specific proteases-3 (cleaved caspase-3), causing the suppression of testicular cell apoptosis. Additionally, melatonin increased the levels of cytochrome P450 17α-hydroxylase/20-lyase (CYP17A1), 17β-hydroxysteroid dehydrogenase 3 (17β-HSD3), and 3β-hydroxysteroid dehydrogenase 4 (3β-HSD4), in the ER, and elevated testosterone levels in testicular tissue. Melatonin can significantly alleviate testicular apoptosis and ER stress induced by BPA, which is because of the upregulation of melatonin receptor expression in testicular cells, inhibition of ER stress-related pathways, and enhancement of testosterone synthesis.