Table 1 Synopsis of key discoveries: Testicular damage due to environmental exposures involves autophagy and oxidative stress disruption.
Classification | Environmental exposure | Animal strains | Exposure concentrations | Exposure routes | Male reproductive toxicity | Potential targets | |
|---|---|---|---|---|---|---|---|
Metal | Cadmium | C57BL/6 mice | 50 mg/L Cd for 3 months | Orally administration | Sperm quality decrease Nuclear depression and deformation Mitochondria damage Autophagy increase | Autophagy: LAMP2, LC3, ATG7, ATG5, Beclin1, P62 | |
Cadmium | SD rats | 0.2 mg/kg, 0.4 mg/kg, 0.8 mg/kg CdCl2 for 5 weeks | Intraperitoneal injection | Sperm quality decrease Testicular architecture damage Testicular cell apoptosis increase Oxidative stress imbalance Autophagy increase | Autophagy: LC3, P62, Beclin-1 | ||
Hexavalent chromium | Wistar rats | 2, 4, and 6 mg/kg body weight K2Cr2O7 for 5 weeks | Intraperitoneal injection | Sperm quality decrease Testicular architecture damage Mitochondria damage DNA damage Oxidative stress imbalance Apoptosis increase Autophagy increase | Autophagy: LC3, P62, Beclin-1 Oxidative stress: Nrf2, Mfn2, HO-1, NQO1, Sirt1, PGC-1α | ||
Metallic nanomaterials | Gold nanoparticles | BALB/c mice | 0.17 mg/kg and 0.5 mg/kg AuNPs for 14 days | Intravenous injection | Plasma testosterone levels reduce Sperm quality decrease Oxidative stress imbalance Autophagy increase | Oxidative stress: IL-1, IL-6, IL-8, TNF-a Autophagy: autophagosome related factors | |
Copper nanoparticles | SD rats | 44, 88, and 175 mg/kg/day nanocopper for 28 days | Oral gavage | Sperm quality decrease Sex hormones decrease Testicular architecture damage Autophagy increase Oxidative stress imbalance | Autophagy: LC3, ATG5, ATG7, ATG12, Beclin1, P62, AKT/mTOR signaling pathway | ||
Air pollutant | Particulate matter | PM2.5 | SD rats | 9 mg/kg.b.w, 24 mg/kg.b.w PM2.5 for 7 weeks | Intratracheally instilled | Sperm quality decrease Testicular architecture damage | Oxidative stress: PI3K/Akt signaling pathway |
Tobacco | Nicotine | SD rats | 0.6 mg/kg nicotine for 28 days | Intraperitoneal injection | Testicular artichitecture damage Spermatogenesis suppress Sperm quality decrease Oxidative stress imbalance | Oxidative stress: SIRT6/Bmal1 regulatory pathway | |
Aldehydes | Formaldehyde | SD rats | 0.5, 5 and 10 mg/m³ formaldehyde 8 h/d for 4 weeks | Inhalation | Testicular seminiferous tubules atrophy Spermatogenic cells decreased Autophagosome increase Damaged and abnormally shaped ER and mitochondria | Oxidative stress: mTOR pathway Autophagy: LC3 | |
Synthetic chemicals | Nano-plastics | BALB/c mice | 100 nm, 5 mg/kg/day or 50 mg/kg/day polystyrene NPs for 30 days | Oral gavage | Sperm quality decrease Testicular architecture damage Apoptosis increase damages the integrity of BTB Impaired autophagy | Autophagy: LC3 and P62 | |
Bisphenol A | BALB/c mice | 5, 20, 50 mg/kg BPA for 30 days | Intraperitoneal injection | Sperm quality decrease Oxidative stress imbalance Endocrine disorder Apoptosis increase Autophagic flux blocked Autophagosome accumulation | Autophagy: LC3, ATG7, P62 Oxidative stress: GPX5, SOD1, SOD2, and CAT | ||
Di-(2-ethylhexyl) phthalate | SD rats | 250 and 500 mg/kg DEHP from postnatal day (PND) 1 to PND 35 | Intragastric administration | Testicular architecture damage Oxidative stress imbalance Autophagosome accumulation | Autophagy: autophagosome LC3 and P62 Oxidative stress: HO-1 and SOD | ||
Perfluorooctane sulfonate | ICR mice | 0.5, 5, and 10 mg/kg/day PFOS for 5 weeks | Gavage | Sperm quality decrease Serum testosterone levels decrease Testicular architecture damage Autophagy increase | Autophagy: PI3K/AKT/mTOR pathway, P62, ATG5, ATG7, and LC3 | ||
Perfluorooctanoic acid | BABL/c mice | 1.25, 5, and 20 mg/kg/d PFOA for 28 days | Gavage | Testicular architecture damage Autophagic flux blocked Autophagosome accumulation | Autophag: LC3, Beclin1 and P62 | ||
Perfluorooctanoic acid | Kunming mice | 2.5, 5 or 10 mg/kg/day PFOA for 14 days | Orally administrated | Sperm quality decrease Testicular architecture damage Oxidative stress imbalance Apoptosis increase | Oxidative stress: NRF2, P53 | ||
4-Nonylphenol | SD rats | 25, 50 or 100 mg/kg 4-NP body weight for 20 days | Intraperitoneal injection | Impaired spermatogenesis and sperm function Sex hormones deficiency Oxidative stress imbalance Apoptosis increase Autophagy increase | Oxidative stress: P53 Autophagy: Beclin-1,LC3, ATG3, ATG5, ATG7, ATG12, AMPK-mTOR-p70S6K/4EBP1 signaling pathway | ||
Acrylamide | SD rats | 40 mg/kg Acrylamide for 10 days | Intraperitoneal injection | Testicular architecture damage Sex hormones decrease Oxidative stress imbalance Apoptosis increase | Oxidative stress: MAPK14 and P53 | ||
Pesticide | Insecticides | Cyfluthrin | Wistar rats | 6.25, 12.5, 25 mg/kg bw Cyfluthrin for 4 weeks | Gavage | Testicular architecture damage Autophagy increase Oxidative stress imbalance | Autophagy: AMPK/mTOR/P70S6K signal pathway |
Insecticides | Avermectin/ Abamectin | SD rats | 1 mg/kg/day ABM for 28 days | Orally administration | Oxidative stress imbalance ER stress Autophagy increase Apoptosis increase | Autophagy: MAPK14/IL-6/JAK2/STAT3 pathway | |
Herbicides | Fluorochloridone | C57BL/6 mice | 3, 15, 75, 375 mg/kg/day Fluorochloridone for 28 days | Gavage | Sperm quality decrease Autophagy increase | Autophagy: LC3, Beclin-1 and P62, AKT/mTOR signaling pathways | |
Fungicides | Thiram | Kunming mice | 30, 60, 120 mg/kg Thiram for 21 days | Oral gavage | Testicular architecture damage Autophagy increase Oxidative stress imbalance | Autophagy: mTOR and P62 | |
