Table 2 Examples of pharmacological compounds or therapeutical procedures found to improve male fertility in different toxicity models by modulating the autophagy process
Drug/ compound/ procedure | Toxicity model | Cell line | Animal model | Target pathway(s) | Effect on autophagy | Finding(s) | Ref(s) |
|---|---|---|---|---|---|---|---|
Rapamycin | ZEA cytotoxicity | Rat Leydig cells | - | mTOR pathway (well-known target of Rapamycin) | ↑ | At various dosages, ZEA effectively decreased Leydig cell proliferation by triggering apoptosis. Autophagy induction using rapamycin reduced apoptosis and protected rat Leydig cells from ZEA cytotoxicity. | [141] |
Naringenin | Cd toxicity | - | Rat | - | ↓ | Cd toxicity can result in pathological changes in rat testicular histopathology, oxidative stress (OS), and marked decreases in serum concentrations of GnRH, FSH, LH, and testosterone. Cd toxicity also leads to the over-expression of autophagy-related proteins, P62 and LC3 II, in the testis. Administration of flavonoid naringenin (50 mg/kg, orally) was shown to protect rat testicular tissue against cadmium-induced damage, at least partly through suppressing Cd-induced autophagy. | [142] |
SIP | Acrolein-induced cytotoxicity | Mouse Leydig cells | - | p38 MAPK and PI3K/Akt pathway | ↓ | SIP was shown to alleviate acrolein-induced cytotoxicity in mouse Leydig cells by suppressing autophagy and apoptosis, further confirming the opposing dual functions of autophagy | [204] |
Resveratrol | Nicotine-induced oxidative damage | Mouse TM3 Leydig cell | - | AMPK phosphorylation and suppressing mTOR pathway | ↓ | Resveratrol treatment prevented nicotine-induced damage to Leydig cells by inducing autophagy through AMPK phosphorylation and suppressing the mTOR pathway. | [205] |