Table III.
Autophagy in environmental toxicants-induced mammalian testicular cell injury.
| Toxin (environmental source) | Affected testicular cell | Autophagy- related gene or protein changes | Resulted in testicular pathology | In human/animal/ cell model | Reference |
|---|---|---|---|---|---|
| DEHP | Leydig cells | LC3-II, Atg5, Beclin 1↑ | Decrease serum testosterone, induce oxidative stress and cell apoptosis | Kunming mice | Sun et al. (2018) |
| GC-1 cells | LC3-II, Beclin 1, Atg5, LC3-II/ LC3-I↑ | Induce oxidative stress, increase autophagic vacuoles number | Mouse GC-1 spg cell line | Gan et al. (2020) | |
| Bisphenol A and nonylphenol | Leydig cells and sperm | Beclin 1, Atg5/12, LC3↑ | Induce spermatogenic epithelium atrophy, germ cell loss, changes of hormones in serum and oxidative stress | Prepubertal Sprague Dawley rats | Su et al. (2018) |
| Copper | GC-1 cells | Atg3, Atg5, p62, LC3-II/LC3-I, Beclin 1, Atg5, p62↑ | Alter cell viability and morphology, induce oxidative stress-mediated mitochondrial dysfunction | Mouse GC-1 spg cell line | Kang et al. (2019) |
| Aflatoxin B1 | Leydig cells and sperm |
LC3, Beclin 1, Atg5, p62↑ p-mTOR/mTOR↓ |
Reduce serum testosterone level, impair sperm, induce the atrophic seminiferous tubules, vacuole-like changes of spermatogenic epithelium, and oxidative stress | Kunming mice | Huang et al. (2019) |
| Leydig cells | LC3, Beclin 1, p62↑ | lower serum T, LH and FSH levels, reduce Leydig cell number | Sprague Dawley rats | Chen et al. (2019b) | |
| Cisplatin | Leydig cells | LC3-II, Atg5↑ | Inhibit cell proliferation and vitality | MLTC-1 cell line | Yang et al. (2018) |
| TOCP | Leydig TM3 cells | LC3-II/LC3-I, Atg5, Beclin 1 ↑ | Inhibit cell viability and testosterone output, increase autophagic vacuoles and oxidative stress | Mouse Leydig TM3 cell line | Liu et al. (2016) |
| SSCs | LC3-II/LC3-I, Atg5, Beclin 1 ↑ | Inhibit viability and proliferation of rat SSCs | Primary SSCs of rats | Liu et al. (2015) | |
| Fluoride | Sertoli cells |
Beclin 1, p62↑ LC3, Atg5↓ |
No significant morphological alterations | Primary Sertoli cells of mice | Feng et al. (2019) |
| Leydig cells | LC3, Beclin 1, Atg5↑ | Increase autophagosomes number | Kunming mice | Zhang et al. (2017) | |
| 4-Nonylphenol | Sertoli cells |
Beclin 1, Atg3/5/7/12↑ LC3-II/LC3-I↑ |
Stimulate the formation of autophagosomes | Sprague Dawley rats | Duan et al. (2017) |
| SCOTP | SSCs | LC3-II/LC3-I, Atg5, Beclin 1↑ | Decrease cell viability and increase autophagic vacuoles | Primary SSCs of rats | Xu et al. (2016) |
| Arsenic | Leydig tumor cells | LC3, Atg7, Beclin 1, Vps34↑ | Impair lysosomes function and induce accumulation of autophagosomes | MLTC-1 | Liang et al. (2020) |
| Zinc oxide nanoparticles | Leydig cells | LC3-II, Atg5, Beclin 1↑ | Disrupt seminiferous epithelium, decrease sperm density and serum testosterone levels | Kunming mice and TM3 cells | Shen et al. (2019) |
| Methyl mercury | Sperm |
LC3-II, Beclin 1↑ p-mTOR/mTOR↓ |
Reduce sperm count and motility, impair the seminiferous tubule, induce apoptosis and oxidative stress | Sprague Dawley rats | Chen et al. (2019a) |
| Nicotine | Leydig cells | Beclin 1, LC3B↑ | Induce serum testosterone reduction and more autophagosomes | C57BL/6 J mice and TM3 cells | Zhao et al. (2018) |
| Cadmium | SSCs | Beclin 1, LC3B↑ | Increase testicular organ coefficients, seminiferous tubular atrophy, SSCs falling off the inner lining, reduce germ cell layers of disorderly arrangements | Wistar rats | Wang et al. (2017) |
| Spermotogonium, Sertoli/ Leydig cells, primary/second spermatocytes, GC-1/GC-2/TM3/TM4 cells |
Beclin 1, LC3-II/LC3-I↑ p-mTOR/mTOR (in vivo)↓ |
Reduce sperm count and motility, impair the seminiferous tubule, induce autophagy, apoptosis and oxidative stress | Sprague Dawley rats, GC-1/GC-2/TM3/TM4 cells | Wang et al. (2020) | |
| Acrolein | Leydig cells | Beclin 1↑ | Suppress proliferation and viability of Leydig cells, decrease testosterone, stimulate autophagy | Primary Leydig cells of mice | Gu et al. (2017) |
DEHP, di-2-ethyl hexyl phthalate; GC-1 cells, mouse spermatogonial cell lines; GC-2 cells, mouse spermatocyte cell lines; MLTC-1, mouse Leydig tumor cell lines; mTOR, mammalian target of rapamycin; SCOTP, saligenin cyclic-O-tolyl phosphate; SSCs, spermatogonial stem cells; TM3 cells, mouse Leydig cell lines; TM4 cells, mouse Sertoli cell lines; TOCP, tri-ortho-cresyl phosphate.