Psychological stress stands as a prevalent form of stress that significantly influences both the physical and mental well-being of healthy individuals. As research delves deeper into this realm, the pathogenic mechanisms underlying psychological stress have gradually come to light, particularly its detrimental effects on sperm motility. Notably, oxidative stress has emerged as a pivotal factor in male infertility, and the excessive generation of reactive oxygen species (ROS) is a well-documented consequence of psychological stress, occurring either directly or indirectly. Drawing upon the intricate interplay between these three phenomena, this review offers a comprehensive overview, reinforcing the hypothesis that psychological stress in males can adversely affect sperm motility by eliciting oxidative stress in vivo through the overproduction of ROS. By elucidating this connection, we aim to provide insights into the potential mechanisms that underlie the negative impact of psychological stress on male reproductive health.

• Psychological stress
• Sperm motility
• Oxidative stress
• Endocrine
• Immunity

 Zhao Y, Zhao X, Yan L, Zhang G, Ma R, et al. (2024) Impact of Psychological Stress on Sperm Motility via Oxidative Stress: A Review. JSM Sexual Med 8(4): 1142.

Stress is a multifaceted concept, encompassing transient or enduring stimuli stemming from both internal and external adverse occurrences. These stimuli can abruptly disrupt the delicate balance of an organism, triggering a cascade of compensatory mechanisms [1-3]. Among the myriad forms of stress-encompassing physical, social, and psychological- psychological stress has garnered significant research attention due to its potential to precipitate a wide array of health conditions [4]. Psychological stress arises when an individual is continually exposed to environmental pressures that surpass their innate coping abilities [4]. Notably, acute stress, often triggered by intense pressure or demands, represents a prevalent subtype of psychological stress [5]. However, when acute stress persists unchecked, leading to a relentless succession of negative events, it can morph into chronic stress. Chronic stress, in turn, accumulates over time, predisposing organs and systems to abnormalities or dysfunction [2,6-9]. Furthermore, psychological stress can manifest its pathogenicity through lifestyle modifications [10,11], which can inadvertently foster the production of reactive oxygen species (ROS) [12,13]. ROS, being highly reactive molecules, can inflict oxidative damage on cellular components, contributing to the deterioration of health and potentially facilitating the onset of various diseases. Thus, the intricate relationship between psychological stress, lifestyle changes, and ROS generation underscores the importance of addressing psychological stress as a critical factor influencing overall health and wellbeing.

It is well established that a physiological level of reactive oxygen species (ROS) within the body is vital for maintaining normal metabolic processes and facilitating diverse molecular pathways [14]. However, when ROS production surpasses the capacity of the antioxidant defense system, an imbalance ensues, leading to oxidative stress (OS). This condition can inflict damage on biological systems, disrupting their normal functioning [15].

Sperm motility is paramount for the successful transport of male gametes to the Fallopian tube’s ampulla, a crucial step in fertilization. Additionally, optimal sperm motility is essential for the effectiveness of intrauterine insemination and in vitro fertilization procedures [16]. Notably, asthenozoospermia, a condition characterized by reduced sperm motility, accounts for approximately 30% of male infertility cases [17]. In the absence of other known pathogenic factors (such as infection, radiation, pollution, or genetic abnormalities), asthenozoospermia can be directly attributed to the presence of OS in the male reproductive tract and organs [18].

Research suggests that psychological stress triggers the generation of ROS, and excessive ROS accumulation ultimately leads to an OS state within the body. Importantly, OS has been shown to compromise sperm motility. Given this backdrop, the question arises: Can psychological stress, directly or indirectly, impact sperm motility via oxidative stress? While a previous study [19] delved into the endocrine-mediated effects of psychological stress on male infertility, this review aims to provide a comprehensive overview and present compelling evidence supporting the hypothesis that psychological stress can adversely affect sperm motility, primarily through the induction of oxidative stress.

In general, negative affective states, such as anxiety and depression, can precipitate stressful events that contribute to the development of physical illnesses and subsequently pose potential risks by directly influencing biological processes or behavioral patterns [4]. Extensive research underscores the connection between the pathogenicity of psychological stress and oxidative stress (OS). The physiological production of reactive oxygen species (ROS) within the body is essential for the normal progression of biological processes [20]. The delicate balance between ROS production and elimination is crucial for maintaining the proper functioning of cells, tissues, organs, and systems. However, when this balance is disrupted, excess ROS or inadequate antioxidant defenses can trigger oxidative stress [21].

Lifestyle modifications induced by psychological stress, including increased alcohol consumption, cigarette smoking, and irregular sleep patterns, can exacerbate ROS generation [22-24]. Additionally, the direct impact of psychological stress on the organism accelerates ROS release, targeting vulnerable tissues and organs, leading to metabolic dysfunction and inhibition of enzymatic antioxidants [25,26]. Notably, prolonged exposure to psychological stress has been associated with elevated levels of blood biomarkers indicative of OS, which can damage lipid cells and RNA [27].

Malondialdehyde (MDA), a product of lipid oxidation, serves as a crucial indicator of the extent or progression of OS in biomedical research. Studies have shown that long-term work- related psychological stress can significantly elevate serum MDA levels, reaching four times higher than those observed in the general population [28]. Similarly, exam stress, a prevalent form of psychological stress, has been found to markedly increase serum MDA levels among university students [29]. These findings underscore the detrimental effects of psychological stress on oxidative stress levels and its subsequent impact on biological systems.

Furthermore, not only the abnormal elevation of MDA levels but also insufficient or aberrant secretion of endogenous antioxidants is indicative of the onset of oxidative stress (OS) [30]. Psychological stress-induced OS not only manifests through elevated MDA levels but also has a proven impact on the secretion and function of antioxidants or antioxidant systems. Superoxide dismutase (SOD), a vital endogenous antioxidant enzyme, effectively shields intracellular targets like proteins, lipids, and DNA from ROS-mediated damage [31]. Animal studies have revealed that, paradoxically, psychological stress was associated with lower MDA levels in specific brain regions of rats compared to controls [32,33]. This phenomenon was also observed in other peripheral tissues and systems, such as the liver, uterus, and blood, where reduced MDA levels were induced by psychological stress [34-36]. Catalase, another crucial endogenous antioxidant, maintains oxidative balance by catalyzing the decomposition of hydrogen peroxide into water and oxygen within cells [37]. Research has demonstrated that psychological stress can diminish catalase levels in the liver and lungs [38], leading to oxidative stress in these tissues. Similarly, the testicular tissue of adult male rats exposed to psychological stress exhibited decreased catalase levels, contributing to oxidative stress in this organ [39]. These findings highlight the intricate interplay between psychological stress, oxidative stress, and the intricate antioxidant mechanisms within the body.

The plasma membranes of spermatozoa are enriched with polyunsaturated fatty acids, while their cytoplasm lacks adequate scavenging enzymes [40], rendering sperm highly vulnerable to oxidative stress (OS)-induced damage. Notably, sperm mitochondria, which fuel sperm motility, are disproportionately susceptible to OS-mediated damage compared to nuclear DNA in human tissues [41]. Impaired mitochondria, targeted by reactive oxygen species (ROS), fail to efficiently produce ATP, exacerbating oxidative stress and contributing to asthenospermia, a condition characterized by reduced sperm motility [42]. Moreover, abnormalities in the sperm flagellum’s motility apparatus structure and dysfunction of motility-related signaling pathways have been implicated in OS [43].

While moderate ROS production is essential for sperm function, excessive ROS generation, triggered by various physical, chemical, and biological factors, can overwhelm sperm’s elimination mechanisms, leading to dysfunction and compromised fertilizing potential [44-46]. The primary endogenous sources of ROS in semen can be broadly categorized into two: immature sperm and leukocytes [47,48]. During spermatogenesis, a proportion of germ cells fail to mature into functional sperm, retaining substantial cytoplasm that harbors high levels of glucose-6-phosphate dehydrogenase, a key enzyme regulating NADPH production via the hexose monophosphate shunt [49,50]. NADPH, in turn, fuels ROS generation through sperm membrane-bound NADPH oxidase [51,52]. Leukocytes, another significant ROS source, are typically present in low numbers in ejaculated semen. However, reproductive tract infections or immune responses can elevate leukocyte concentrations, with activated leukocytes producing up to 1000 times more ROS than spermatozoa [50,53].

Exogenous ROS sources encompass smoking, alcohol consumption, and other lifestyle factors [54-56], further compounding the oxidative burden on sperm and potentially impacting fertility outcomes.

Indeed, psychological stress has been documented to elevate reactive oxygen species (ROS) levels within the body, thereby precipitating oxidative stress (OS). Given that OS is a pivotal factor influencing sperm motility, and numerous studies have implicated psychological stress as a potential contributor to male infertility [19,55], we posit a hypothesis that psychological stress diminishes sperm motility by instigating OS.

Endocrine Regulation

As is well established, cortisol serves as the terminal product of the hypothalamic-pituitary-adrenal (HPA) axis. The initiation of psychological stress stimulates the hypothalamus, which prompts the release of corticotrophin-releasing hormone (CRH). This, in turn, triggers the pituitary gland to secrete adrenocorticotropic hormone (ACTH). Subsequently, under this physiological cascade, the adrenal gland’s cortex elevates cortisol secretion levels [57]. The intricate interplay between psychological stress and HPA axis activity is well documented [58], with persistent stress leading to HPA axis dysfunction and aberrant hormone secretion. Specifically, sustained stress augments CRH release, fostering a continual surge in ACTH secretion by the pituitary gland, ultimately augmenting serum cortisol concentrations.

Circulating cortisol exists in both free and bound forms, with the free cortisol molecule, due to its lipophilic nature and low molecular weight, effortlessly traversing blood capillaries into tissues [57]. Notably, free cortisol exhibits heightened biological activity [59]. Intriguingly, a U-shaped correlation exists between cortisol and mitochondrial function [60], implying that cortisol levels are intimately tied to ROS generation and the initiation of oxidative stress. Consequently, excessive cortisol concentrations can inflict oxidative stress-mediated damage and impair cellular functions, encompassing spermatozoa.

Preceding investigations have also illuminated the adverse impact of stress on testicular function via cortisol mediation [61-63]. Specifically, high concentrations of serum-free cortisol infiltrate the epididymis via capillaries, assaulting mitochondrial structures within spermatozoa. This process continually amplifies ROS concentrations, leading to aberrant mitochondrial function, and consequently, diminished sperm motility [Figure 1]. Thus, the intricate interplay between psychological stress, cortisol dysregulation, and oxidative stress emerges as a pivotal determinant of sperm health and male fertility.

Immunity Regulation

Leukocytospermia, as defined by the World Health Organization (WHO), refers to the presence of over 1×10^6 leukocytes per milliliter of ejaculate [64]. These leukocytes in semen, primarily originating from the prostate, have been implicated in compromising sperm motility [65]. Accumulation of a significant number of leukocytes has been shown to foster heightened production of reactive oxygen species (ROS), as evidenced by numerous studies [66-68]. This extrinsic generation of ROS by leukocytes can assault sperm mitochondria, ultimately leading to decreased sperm motility [69].

Psychological stress stands as a prevalent pathogenic factor contributing to the onset and progression of chronic prostatitis [70-72]. Prolonged exposure to stress stimuli significantly alters the histopathology of the prostate gland, characterized by convoluted acini lined with reduced secretory activity, heightened epithelial cell activity, and a substantial influx of inflammatory cells [73]. Additionally, psychological stress disrupts the cytokine balance within the prostate gland, with pro-inflammatory factors such as IL-6 and IL-10 positively correlated with stress levels [72].

A recent investigation [74] has revealed that psychological stress activates both the HPA axis and the sympathetic nervous system (SNS), thereby modulating the immune response in the prostate gland by upregulating the expression of inflammatory factor genes. Consequently, the HPA axis and SNS, when activated by psychological stress, likely elevate inflammatory factor levels in the prostate gland, precipitating inflammatory changes. These inflammatory changes, in turn, generate leukocytes-pathological byproducts-which produce an abundance of ROS, triggering oxidative stress and ultimately diminishing sperm motility [Figure 1].

Figure 1 The schematic diagram illustrates the intricate interplay between psychological stress and sperm motility. Psychological stress, either directly or indirectly, triggers the generation of reactive oxygen species (ROS), thereby inducing oxidative stress. This process is further exacerbated by the imbalance of the hypothalamic- pituitary-adrenal (HPA) axis, which leads to an elevation in the secretion of free cortisol. Elevated levels of free cortisol subsequently target the mitochondria in spermatozoa, provoking the release of ROS and initiating oxidative stress. Concurrently, psychological stress augments the production of pro-inflammatory factors, stimulating the prostate to secrete an abundance of leukocytes. These leukocytes, in turn, generate high levels of ROS, contributing to oxidative stress. Additionally, the lifestyle changes prompted by psychological stress indirectly contribute to the accumulation of ROS in the body, ultimately diminishing sperm motility.

Alcohol Consumption

Alcohol consumption often emerges as a significant lifestyle alteration in response to chronic psychological stress, serving as a means to alleviate stress stimuli and alleviate feelings of distress, which can be a pivotal trigger for alcohol use [75]. Research has consistently demonstrated that males who consume alcohol exhibit lower sperm motility compared to those who abstain [76- 78]. Furthermore, alcohol intake has been confirmed to induce oxidative stress in vivo, primarily through ethanol metabolism, which gives rise to the generation of reactive oxygen species (ROS) and reactive nitrogen species, while simultaneously diminishing antioxidant activity [79].

The detrimental effects of alcohol extend directly to the testis, causing dysfunction in the seminiferous tubules and epididymis. Consequently, chronic alcohol consumption fueled by psychological stress exacerbates these toxic effects, potentially targeting the testis and epididymis. This, in turn, leads to heightened levels of metabolic ROS, triggering oxidative stress responses that ultimately impair sperm motility [Figure 1].

Cigarette Smoking

Cigarette smoking is another prevalent behavioral adaptation to psychological stress, often employed as a coping mechanism to alleviate cumulative negative stress at the psychosocial level [80,81]. Renowned as a significant pathogenic factor in numerous diseases, smoking can induce tissue and organ dysfunction by generating excessive reactive oxygen species (ROS), which constitutes a pivotal pathogenic pathway [82,83].

Among smokers, a heightened level of leukocytospermia is commonly observed, signifying the presence of excessive ROS or oxidative stress, which is directly linked to cigarette smoking [84]. The diverse compounds present in cigarette ingredients and smoking metabolites act as potent chemotactic stimuli, triggering the inflammatory response. This, in turn, leads to the proliferation of leukocytes and the subsequent generation of ROS [84,85].

Ultimately, cigarette smoking adversely affects male semen quality, with sperm motility being particularly vulnerable to its detrimental effects [86] [Figure 1].

Psychological stress can elicit a myriad of physiological alterations, significantly impacting the functionality of tissues and organs. Recent studies have unveiled novel pathways and mechanisms that elucidate the pathological role of psychological stress. While this review on the mechanisms underlying the direct or indirect effects of psychological stress on sperm motility is largely speculative, the linkage between psychological stress, oxidative stress, and sperm motility stands firm. Consequently, there is a pressing need for more exhaustive and rigorously designed epidemiological studies and fundamental research to fortify and explicate this intricate relationship. This novel insight potentially heralds a new direction in the investigation of idiopathic male infertility. Similarly, elucidating the correlation between psychological stress and sperm motility may offer innovative therapeutic strategies for addressing male infertility. By acknowledging the interplay between these factors, we can pave the way for more targeted and effective interventions in the field of reproductive health.

This work is supported by the National Key Research and Development program (2017YFC1311103) and the Science & Technology Development Fund of Tianjin Education Commission for Higher Education (2022KJ166).

1. Bae YS, Shin EC, Bae YS, Van Eden W. Editorial: Stress and Immunity. Front Immunol. 2019; 10: 245.
2. Knauft K, Waldron A, Mathur M, Kalia V. Perceived chronic stress influences the effect of acute stress on cognitive flexibility. Sci Rep. 2021; 11: 23629.
3. Chrousos GP, Gold PW. The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. JAMA. 1992; 267: 1244-1252.
4.   Cohen S, Janicki-Deverts D, Miller GE. Psychological stress and disease. JAMA. 2007; 298: 1685-1687.
5. Prasad S, Tiwari M, Pandey AN, Shrivastav TG, Chaube SK. Impact of stress on oocyte quality and reproductive outcome. J Biomed Sci. 2016; 23: 36.
6. Bräuner EV, Nordkap L, Priskorn L, Hansen ÅM, Bang AK, Holmboe SA, et sl. Psychological stress, stressful life events, male factor infertility, and testicular function: a cross-sectional study. Fertil Steril. 2020; 113: 865-875.
7. Qin HY, Cheng CW, Tang XD, Bian ZX. Impact of psychological stress on irritable bowel syndrome. World J Gastroenterol. 2014; 20: 14126-14131.
8. Krantz DS, McCeney MK. Effects of psychological and social factors on organic disease: a critical assessment of research on coronary heart disease. Annu Rev Psychol. 2002; 53: 341-369.
9. Allen JM, Mackos AR, Jaggers RM, Brewster PC, Webb M, Lin CH, etal. Psychological stress disrupts intestinal epithelial cell function and mucosal integrity through microbe and host-directed processes. Gut Microbes. 2022; 14: 2035661.
10. Veenstra MY, Lemmens PH, Friesema IH, Tan FE, Garretsen HF, Knottnerus JA, et al. Coping style mediates impact of stress on alcohol use: a prospective population-based study. Addiction. 2007, 102: 1890-1898. Ogden J, Stavrinaki M, Stubbs J. Understanding the role of life events in weight loss and weight gain. Psychol Health Med. 2009. 14: 239-249.
11. Møller P, Wallin H, Knudsen LE. Oxidative stress associated with exercise, psychological stress and life-style factors. Chem Biol Interact. 1996; 102: 17-36.
12. Görlach A, Dimova EY, Petry A, Martínez-Ruiz A, Hernansanz-Agustín P, et al. Reactive oxygen species, nutrition, hypoxia and diseases: Problems solved?. Redox Biol. 2015; 6: 372-385.
13. Bayir H. Reactive oxygen species. Crit Care Med. 2005; 33: 498-501.
14. Forman HJ, Zhang H. Targeting oxidative stress in disease: promise and limitations of antioxidant therapy. Nat Rev Drug Discov. 2021; 20: 689-709.
15. Nowicka-Bauer K, Nixon B. Molecular Changes Induced by Oxidative Stress that Impair Human Sperm Motility. Antioxidants (Basel). 2020; 9: 134.
16. Liu FJ, Liu X, Han JL, Wang YW, Jin SH, Liu XX, et al. Aged men share the sperm protein PATE1 defect with young asthenozoospermia patients. Hum Reprod. 2015; 30: 861-869.
17. Nowicka-Bauer K, Lepczynski A, Ozgo M, Kamieniczna M, Fraczek M, Stanski L, et al. Sperm mitochondrial dysfunction and oxidative stress as possible reasons for isolated asthenozoospermia. J Physiol Pharmacol. 2018; 6 9.
18. Nargund VH. Effects of psychological stress on male fertility. Nat Rev Urol. 2015; 12: 373-382.
19. Mhamdi A, Van Breusegem F. Reactive oxygen species in plant development. Development. 2018; 145.
20. Kohen R, Nyska A. Oxidation of biological systems: oxidative stress phenomena, antioxidants, redox reactions, and methods for their quantification. Toxicol Pathol. 2002; 30: 620-650.
21. Wang Y, Zhao J, Yang W, Bi Y, Chi J, Tian J, et al. High-dose alcohol induces reactive oxygen species-mediated apoptosis via PKC-β/ p66Shc in mouse primary cardiomyocytes. Biochem Biophys Res Commun. 2015; 456: 656-61.
22. Dechanet C, Anahory T, Mathieu Daude JC, Quantin X, Reyftmann L, Hamamah S, et al. Effects of cigarette smoking on reproduction. Hum Reprod Update. 2011; 17: 76-95.
23. Aghelan Z, Karima S, Khazaie H, Abtahi SH, Farokhi AR, Rostampour M, et al. Interleukin-1α and tumor necrosis factor α as an inducer for reactive-oxygen-species-mediated NOD-like receptor protein 1/NOD-like receptor protein 3 inflammasome activation in mononuclear blood cells from individuals with chronic insomnia disorder. Eur J Neurol. 2022; 29: 3647-3657.
24. Wang L, Muxin G, Nishida H, Shirakawa C, Sato S, Konishi T. Psychological stress-induced oxidative stress as a model of sub- healthy condition and the effect of TCM. Evid Based Complement Alternat Med. 2007; 4: 195-202.
25. Salim S. Oxidative stress and psychological disorders. CurrNeuropharmacol. 2014; 12: 140-147.
26. Aschbacher K, O’Donovan A, Wolkowitz OM, Dhabhar FS, Su Y,Epel E. Good stress, bad stress and oxidative stress: insights fromanticipatory cortisol reactivity. Psychoneuroendocrinology. 2013; 38: 1698-1708.
27. Salem EA, Ebrahem SM. Psychosocial work environment andoxidative stress among nurses’. J Occup Health. 2018; 60: 182-191.
28. Nakhaee A, Shahabizadeh F, Erfani M. Protein and lipid oxidative damage in healthy students during and after exam stress. Physiol Behav. 2013; 118: 118-121.
29. Forman HJ, Zhang H. Targeting oxidative stress in disease: promise and limitations of antioxidant therapy. Nat Rev Drug Discov. 2021; 20: 689-709.
30. Islam MN, Rauf A, Fahad FI, Emran TB, Mitra S, Olatunde A, et al. Superoxide dismutase: an updated review on its health benefits and industrial applications. Crit Rev Food Sci Nutr. 2022; 62: 7282-7300.
31. Yu S, Feng Y, Shen Z, Li M. Diet supplementation with iron augments brain oxidative stress status in a rat model of psychological stress. Nutrition. 2011; 27: 1048-1052.
32. Kamper EF, Chatzigeorgiou A, Tsimpoukidi O, Kamper M, Dalla C, Pitychoutis PM, et al. Sex differences in oxidant/antioxidant balance under a chronic mild stress regime. Physiol Behav. 2009; 98: 215- 222.
33. Zhu X, Hu S, Zhu L, Ding J, Zhou Y, Li G. Effects of Lycium barbarum polysaccharides on oxidative stress in hyperlipidemic mice following chronic composite psychological stress intervention. Mol Med Rep. 2015; 11: 3445-3450.
34. Novío S, Núñez MJ, Amigo G, Freire-Garabal M. Effects of fluoxetine on the oxidative status of peripheral blood leucocytes of restraint- stressed mice. Basic Clin Pharmacol Toxicol. 2011; 109: 365-371.
35. Han J, Yang D, Liu Z, Tian L, Yan J, Li K, et al. The damage effect of heat stress and psychological stress combined exposure on uterus in female rats. Life Sci. 2021; 286: 120053.
36. Nandi A, Yan LJ, Jana CK, Das N. Role of Catalase in Oxidative Stress- and Age-Associated Degenerative Diseases. Oxid Med Cell Longev. 2019; 2019: 9613090.
37. Toleikis PM, Godin DV. Alteration of antioxidant status in diabetic rats by chronic exposure to psychological stressors. Pharmacol Biochem Behav. 1995; 52: 355-366.
38. Yadav A, Yadav K, Rajpoot A, Lal B, Mishra RK. Sub-chronic restraint stress exposure in adult rats: An insight into possible inhibitory mechanism on testicular function in relation to germ cell dynamics. Andrologia. 2022: 14575.
39. Agarwal A, Saleh RA, Bedaiwy MA. Role of reactive oxygen species in the pathophysiology of human reproduction. Fertil Steril. 2003; 79: 829-843.
40. Amaral S, Oliveira PJ, Ramalho-Santos J. Diabetes and the impairment of reproductive function: possible role of mitochondria and reactive oxygen species. Curr Diabetes Rev. 2008; 4: 46-54.
41. Nowicka-Bauer K, Nixon B. Molecular Changes Induced by Oxidative Stress that Impair Human Sperm Motility. Antioxidants (Basel). 2020; 9: 134.
42. Baker MA, Weinberg A, Hetherington L, Villaverde AI, Velkov T, Baell J, et al. Defining the mechanisms by which the reactive oxygen species by-product, 4-hydroxynonenal, affects human sperm cell function. Biol Reprod. 2015; 92: 108.
43. Blumer CG, Restelli AE, Giudice PT, Soler TB, Fraietta R, Nichi M, et al. Effect of varicocele on sperm function and semen oxidative stress. BJU Int. 2012; 109: 259-265.
44. Rafiee Z, Rezaee-Tazangi F, Zeidooni L, Alidadi H, Khorsandi L. Protective effects of selenium on Bisphenol A-induced oxidative stress in mouse testicular mitochondria and sperm motility. JBRA Assist Reprod. 2021; 25: 459-465.
45. Chen SJ, Allam JP, Duan YG, Haidl G. Influence of reactive oxygen species on human sperm functions and fertilizing capacity including therapeutical approaches. Arch Gynecol Obstet. 2013; 288:191-199.
46. Gomez E, Buckingham DW, Brindle J, Lanzafame F, Irvine DS, Aitken RJ. Development of an image analysis system to monitor the retention of residual cytoplasm by human spermatozoa: correlation with biochemical markers of the cytoplasmic space, oxidative stress, and sperm function. J Androl. 1996; 17: 276-287.
47. Agarwal A, Rana M, Qiu E, AlBunni H, Bui AD, Henkel R. Role of oxidative stress, infection and inflammation in male infertility. Andrologia. 2018; 50: 13126.
48. Patil PS, Humbarwadi RS, Patil AD, Gune AR. Immature germ cells in semen - correlation with total sperm count and sperm motility. J Cytol. 2013; 30: 185-189.
49. Barati E, Nikzad H, Karimian M. Oxidative stress and male infertility: current knowledge of pathophysiology and role of antioxidant therapy in disease management. Cell Mol Life Sci. 2020; 77: 93-113.
50. Gomez E, Buckingham DW, Brindle J, Lanzafame F, Irvine DS, Aitken RJ. Development of an image analysis system to monitor the retention of residual cytoplasm by human spermatozoa: correlation with biochemical markers of the cytoplasmic space, oxidative stress, and sperm function. J Androl. 1996; 17: 276-87. Said TM, Agarwal A, Sharma RK, Mascha E, Sikka SC, Thomas AJ Jr. Human sperm superoxide anion generation and correlation with semen quality in patients with male infertility. Fertil Steril. 2004; 82: 871-877.
51. Whittington K, Ford WC. Relative contribution of leukocytes and of spermatozoa to reactive oxygen species production in human sperm suspensions. Int J Androl. 1999; 22: 229-235.
52. Ranganathan P, Rao KA, Thalaivarasai Balasundaram S. Deterioration of semen quality and sperm-DNA integrity as influenced by cigarette smoking in fertile and infertile human male smokers-A prospective study. J Cell Biochem. 2019; 120: 11784-11793.
53. Agarwal A, Baskaran S, Parekh N, Cho CL, Henkel R, Vij S, et al. Male infertility. Lancet. 2021; 397: 319-333.
54. Shefi S, Tarapore PE, Walsh TJ, Croughan M, Turek PJ. Wet heat exposure: a potentially reversible cause of low semen quality in infertile men. Int Braz J Urol. 2007; 33: 50-6; 56-57.
55. Levine A, Zagoory-Sharon O, Feldman R, Lewis JG, Weller A. Measuring cortisol in human psychobiological studies. Physiol Behav. 2007; 90: 43-53.
56. Herman JP, Ostrander MM, Mueller NK, Figueiredo H. Limbic system mechanisms of stress regulation: hypothalamo-pituitary- adrenocortical axis. Prog Neuropsychopharmacol Biol Psychiatry. 2005; 29: 1201-1213.
57. Mendel CM. The free hormone hypothesis: a physiologically basedmathematical model. Endocr Rev. 1989; 10: 232-274.
58. Du J, Wang Y, Hunter R, Wei Y, Blumenthal R, Falke C, Khairova R, et al. Dynamic regulation of mitochondrial function by glucocorticoids. Proc Natl Acad Sci USA. 2009; 106: 3543-3548.Claus R, Wagner A, LambertT. Characterization of 11beta-hydroxysteroid dehydrogenase activity in testicular tissue of control and GnRH-immunized boars as a possible regulator of spermatogenesis. Exp Clin Endocrinol Diabetes. 2005; 113: 262-267.
59. Nacharaju VL, Muneyyirci-Delale O, Khan N. Presence of 11 beta- hydroxysteroid dehydrogenase in human semen: evidence of correlation with semen characteristics. Steroids. 1997; 62: 311-314.
60. Rengarajan S, Balasubramanian K. Corticosterone has direct inhibitory effect on the expression of peptide hormone receptors, 11 beta-HSD and glucose oxidation in cultured adult rat Leydig cells. Mol Cell Endocrinol. 2007; 279: 52-62.
61. World Health Organization. WHO laboratory manual for the examination and processing of human semen. Geneva, Switzerland. WHO. 2010; 5th ed.
62. Wolff H, Bezold G, Zebhauser M, Meurer M. Impact of clinically silent inflammation on male genital tract organs as reflected by biochemical markers in semen. J Androl. 1991; 12: 331-334.
63. Saleh RA, Agarwal A, Kandirali E, Sharma RK, Thomas AJ, Nada EA, et al. Leukocytospermia is associated with increased reactive oxygen species production by human spermatozoa. Fertil Steril. 2002; 78: 1215-1224.
64. Lackner JE, Agarwal A, Mahfouz R, du Plessis SS, Schatzl G. The association between leukocytes and sperm quality is concentration dependent. Reprod Biol Endocrinol. 2010; 8: 12.
65. Henkel R, Offor U, Fisher D. The role of infections and leukocytes in male infertility. Andrologia. 2021; 53: 13743.
66. Henkel R, Kierspel E, Stalf T, Mehnert C, Menkveld R, Tinneberg HR, et al. Effect of reactive oxygen species produced by spermatozoa and leukocytes on sperm functions in non-leukocytospermic patients. Fertil Steril. 2005; 83: 635-642.
67. Miller HC. Stress prostatitis. Urology. 1988; 32: 507-510.
68. Ullrich PM, Turner JA, Ciol M, Berger R. Stress is associated with subsequent pain and disability among men with nonbacterial prostatitis/pelvic pain. Ann Behav Med. 2005; 30: 112-118.
69. Pontari MA, Ruggieri MR. Mechanisms in prostatitis/chronic pelvic pain syndrome. J Urol. 2004; 172: 839-845.
70. Gatenbeck L, Aronsson A, Dahlgren S, Johansson B, Strömberg L.Stress stimuli-induced histopathological changes in the prostate: anexperimental study in the rat. Prostate. 1987; 11: 69-76.
71. Bellinger DL, Dulcich MS, Molinaro C, Gifford P, Lorton D, Gridley DS, et al. Psychosocial Stress and Age Influence Depression and Anxiety-Related Behavior, Drive Tumor Inflammatory Cytokines and Accelerate Prostate Cancer Growth in Mice. Front Oncol. 2021; 11: 703848.
72. Veenstra MY, Lemmens PH, Friesema IH, Tan FE, Garretsen HF, JA Knottnerus, et al. Coping style mediates impact of stress on alcohol use: a prospective population-based study. Addiction. 2007; 102: 1890-1898.
73. Pajarinen J, Karhunen PJ, Savolainen V, Lalu K, Penttilä A, Laippala P. Moderate alcohol consumption and disorders of human spermatogenesis. Alcohol Clin Exp Res. 1996; 20: 332-337.
74. Muthusami KR, Chinnaswamy P. Effect of chronic alcoholism on male fertility hormones and semen quality. Fertil Steril. 2005; 84: 919-924.
75. Yao DF, Mills JN. Male infertility: lifestyle factors and holistic, complementary, and alternative therapies. Asian J Androl. 2016; 18: 410-418.
76. Das SK, Vasudevan DM. Alcohol-induced oxidative stress. Life Sci. 2007; 81: 177-187.
77. Hajek P, Taylor T, McRobbie H. The effect of stopping smoking on perceived stress levels. Addiction. 2010; 105: 1466-1471.
78. Park CL, Iacocca MO. A stress and coping perspective on health behaviors: theoretical and methodological considerations. Anxiety Stress Coping. 2014; 27: 123-137.
79. Halliwell B, Cross CE. Oxygen-derived species: their relation to human disease and environmental stress. Environ Health Perspect. 1994; 102: 5-12.
80. Bhattacharyya A, Chattopadhyay R, Mitra S, Crowe SE. Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol Rev. 2014; 94: 329-354.
81. Saleh RA, Agarwal A, Sharma RK, Nelson DR, Thomas AJ Jr. Effect of cigarette smoking on levels of seminal oxidative stress in infertile men: a prospective study. Fertil Steril. 2002; 78: 491-499.
82. Richthoff J, Elzanaty S, Rylander L, Hagmar L, Giwercman A. Association between tobacco exposure and reproductive parameters in adolescent males. Int J Androl. 2008; 31: 31-39.
83. Gaur DS, Talekar M, Pathak VP. Effect of cigarette smoking on semen quality of infertile men. Singapore Med J. 2007; 48: 119-123