Environmental Factors-Induced Oxidative Stress: Hormonal and Molecular Pathway Disruptions in Hypogonadism and Erectile Dysfunction
Abstract
:1. Introduction
2. Methods
3. Testosterone Metabolism, Spermatogenesis, and Reactive Oxygen Species (ROS)
4. Etiology and Pathogenesis
4.1. Hypogonadism
4.2. Erectile Dysfunction (ED)
5. Environmental Factors
5.1. Pesticides
5.2. Radiation
5.2.1. Nonionizing Radiation
5.2.2. Ionizing Radiation
5.3. Air Pollution
5.3.1. Heavy Metal Pollution
5.3.2. Particulate Matter (PM2.5) Pollution
5.4. Other Endocrine-Disrupting Chemicals
5.4.1. Agents Originating in Plastics
5.4.2. Polychlorinated Biphenyl (PCB)
6. Future Perspectives
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Environmental Factor | Experimental Model | Experimental Type | Exposure Parameters | Findings | Comments | References |
Pesticides | Human | In vivo | Exposure to various pesticides for 2–11 years | Decreased serum testosterone level and LH | Decrease in sperm count and viability | [89] |
Rat | In vivo | Chlorpyrifos at 17.5 mg/kg bodyweight for 30 days | Decrease in serum testosterone level, sperm count and motility, but increase in cholesterol level | High cholesterol level in the testes decrease the androgen level and hampers spermatogenesis | [31] | |
Rat | In vivo | Diazinon at 30 mg/kg body weight at 5 consecutive days for 30 days | Decrease in serum testosterone level | Reduction in sperm count, diameter of seminiferous tubules | [23] | |
Rat | In vivo | 12.5 mg/kg cypermethrin for 12 weeks | Decrease in serum testosterone level | Reduction in testicular weight, sperm count, viability, motility | [110] | |
Radiation | Human | In vivo | Ionizing radiation from external beam radiation therapy (EBRT) for 3 months, at the median 68Gy, as a part of prostate cancer treatment | Decrease in serum testosterone level | Suppression of spermatogenesis | [167] |
Rat | In vivo | Exposure to 900 MHz nonionizing radiation of cell phones | Increase in SOD activity | Production of ROS, lipid peroxidation, damaged spermatozoa | [24] | |
Rat | In vivo | Exposure to 10 GHz non-ionizing radiation of XeThru X4 radar for 90 days | Decrease in serum testosterone and sex-hormone-binding protein | Effect on the male reproductive system | [150] | |
Rat | In vivo | Exposure to 2.45 GHz of non-ionizing radiation | Decrease in serum testosterone level and increase in ROS, NO and MDA levels, expression of p53, Bax and active caspase in testes upregulated, while the expression of Bcl-xL, Bcl-2, procaspase and PARP-1 were downregulated | Decrease in seminiferous tubule diameter, sperm count, sperm motility and viability | [151] | |
Rat | In vivo | Exposure to 7.5 Gy ionizing radiation for 5 days | Decrease in intracavernosal pressure | Reduced potential of attaining and maintaining prolonged penile erection | [170] | |
Rat | In vivo | Exposure to 20 Gy ionizing radiation for 9 weeks | Decrease in intracavernosal pressure, increase in DNA oxidative stress in corpora cavernosa and prostate and increase in lipid peroxidation in corpora cavernosa | Erectile dysfunction may occur | [171] | |
Rat | In vivo | Single dose of 4Gy ionizing radiation from X-rays | Decrease in serum testosterone level | Decrease in sperm count and motility, weight of testes, distortion in the architecture of seminiferous tubules | [172] | |
Rat | In vivo | γ ionizing radiation | Decrease in serum testosterone level, SOD activity and a sharp rise in testicular MDA levels | Induction of oxidative stress | [173] | |
Mice | In vivo | 0.25 Gy ionizing radiation from X-ray twice a day for 4 days | Decrease in testosterone level, glutathione concentration and increase in ROS level, lipid peroxidation, serum LDH activity, antioxidant enzyme activities | Decrease in sperm count and motility. Testicular damage | [174] | |
Air Pollution | Rats | In vivo | 6.5 mg/kg CdCl2 intraperitoneal injection for 5 days | Decrease in Testosterone level, antioxidant enzyme activities, PCNA antigen and increase in Cd concentration, lipid peroxidation, NO and MDA levels. Upregulation of BAX, TNFα factor, downregulation of BCL 2 gene | Decrease in weight of testes, depletion of DNA contents due to oxidative stress | [192] |
Rat | In vivo | 4.28 mg/kg CdCl2 for 7 days | Decrease in serum testosterone concentration, SOD activity | Damage in the epithelium of seminiferous tubules | [193] | |
Rat | In vivo | Single oral supplementation of 10 mg/kg/bodyweight of CdCl2 | Decrease in serum testosterone level, increase in MDA level | Testicular damage due to Cd-induced oxidative stress | [194] | |
Rat | In vivo | 2.5 mg/kg/bodyweight oral supplementation of CdCl2 | Decrease in serum testosterone level, FSH, LH level | Decrease in semen quality parameters and gonadosomatic index | [195] | |
Rat | In vivo | Oral supplementation of 20 mg/kg PbAc for 10 days | Decrease in the levels of serum testosterone, FSH, LH levels, catalase activity and total antioxidant capacity. Increase in lipid peroxidation and levels of three lysosomal enzymes, including ACP, ß-NAG, and β-GAL in testes | Oxidative stress due to increase of ROS in testes. Accumulation of Pb in the testis tissues | [200] | |
Rat | In vivo | 0.1% PbAc in drinking water for 70 days | Decrease in serum testosterone level, SOD and glutathione peroxidase level | Reduction in weight of testes, the diameter of seminiferous tubules, epididymal sperm count | [201] | |
Rat | In vivo | Oral supplementation of 50 mg/kg/bodyweight of Pb for 4 weeks | Decreased testosterone and GnRH level, glutathione, SOD, catalase activity | Imbalance in testosterone, GnRH levels and antioxidant enzymes can lead to male infertility | [202] | |
Rat Leydig cell line R2C | In vitro | Cell lines incubated for 24 h in different concentration of Pb (50, 100, 200, 400 μM) | Decreased production of progesterone (precursor of testosterone), protein expression level of StAR, CYP11A1, 3β-HSD | Pb-induced oxidative stress can change the expression of antioxidant enzymes | [203] | |
Rat | In vivo | Exposure to different concentration of PM2.5 once each week for 6 weeks | Ratio of intracavernosal pressure to mean atrial pressure decreased, ratio of smooth muscles to collagen decreased and ROS production increased | Testicular necrosis, hemorrhage, reduction in testicular size, degeneration of seminiferous tubules | [25] | |
Mice | In vivo | Exposure to concentrated ambient PM2.5 (CAP) | Decrease in sperm count, circulating FSH and testosterone level, hypothalamic GnRH level | Adverse effects on testicular spermatogenesis resulting in sperm alterations | [217] | |
Other endocrine-disrupting chemicals | Human | In vivo | Exposure to BPA from working in factories | Decrease in testosterone level | Reduced sexual function, coitus frequency, inability to achieve an erection, ED | [235] |
Human | In vivo | Workers exposed to BPA in BPA and resin manufacturing companies | Lower sexual functions | Orgasmic function lowered leading to ED | [235] | |
Human | In vivo | Exposure to BPA and BADGE) | Changes in endogenous sex hormone levels elevated urinary BPA concentration | Altered level of estrogen, androgen, gonadotropin, SHBG | [237] | |
Human | In vivo | Exposure to DBP and DEHP in polyvinyl chloride flooring producing factory | High levels of MBP and MEHP in body and decrease in testosterone, FSH, LH level. | Reduction in steroidogenic activity and spontaneous erection that might lead to ED. | [232] | |
Human | In vivo | Exposure to PFAS | Negative association between PFOS with testosterone | Decrease in the testosterone level with no effect on semen quality | [254] | |
Rat | In vivo | Administration of DEHP for 30 days | Affects testicular physiology and testosterone production | Deformation of seminiferous tubules along with an increase in Leydig cell number | [242] | |
Rat | In vivo | Exposure of Leydig cells to different concentrations of PCB | Inhibition of basal and LH-stimulated testosterone production | Testosterone level decreases with decreased the activity of steroidogenic enzymes, enzymatic and nonenzymatic antioxidants | [262] | |
Mice Leydig cell line TM3 | In vitro | DEHP treatment to Leydig cell TM3 for 24 h | Disturbance in the HPG axis | Reduction in LH and FSH level as well as testosterone level | [242] |
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Roychoudhury, S.; Chakraborty, S.; Choudhury, A.P.; Das, A.; Jha, N.K.; Slama, P.; Nath, M.; Massanyi, P.; Ruokolainen, J.; Kesari, K.K. Environmental Factors-Induced Oxidative Stress: Hormonal and Molecular Pathway Disruptions in Hypogonadism and Erectile Dysfunction. Antioxidants 2021, 10, 837. https://doi.org/10.3390/antiox10060837
Roychoudhury S, Chakraborty S, Choudhury AP, Das A, Jha NK, Slama P, Nath M, Massanyi P, Ruokolainen J, Kesari KK. Environmental Factors-Induced Oxidative Stress: Hormonal and Molecular Pathway Disruptions in Hypogonadism and Erectile Dysfunction. Antioxidants. 2021; 10(6):837. https://doi.org/10.3390/antiox10060837
Chicago/Turabian StyleRoychoudhury, Shubhadeep, Saptaparna Chakraborty, Arun Paul Choudhury, Anandan Das, Niraj Kumar Jha, Petr Slama, Monika Nath, Peter Massanyi, Janne Ruokolainen, and Kavindra Kumar Kesari. 2021. "Environmental Factors-Induced Oxidative Stress: Hormonal and Molecular Pathway Disruptions in Hypogonadism and Erectile Dysfunction" Antioxidants 10, no. 6: 837. https://doi.org/10.3390/antiox10060837