Nicotine induced autophagy of Leydig cells rather than apoptosis is the major reason of the decrease of serum testosterone

Zhao, Xianglong; Xu, Wangjie; Wu, Jiajie; Zhang, Dong; Abou-Shakra, Abdelrahman; Di, Ling; Wang, Zhaoxia; Wang, Lianyun; Yang, Fan; Qiao, Zhongdong

doi:10.1016/j.biocel.2018.05.001

Cited by 41 publications

(19 citation statements)

References 38 publications

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“…Leydig cells, as an important part of the testicular stroma, are the main source of androgens [87]. Zhao et al have shown that autophagy induced by suppressing the Akt-mTOR pathway can inhibit Leydig cells, thereby reducing serum testosterone levels [30]. SCs are essential for spermatogenesis and male fertility, and they coordinate the spermatogenesis process by providing nutrition and an environment conducive to the survival and development of germ cells [88][89][90].…”

Section: The Role Of Autophagy In Male Testicular Functionsmentioning

confidence: 99%

“…Therefore, in this review, we speculate that in diabetes, excessive production of ROS can induce autophagy in the testis. A series of studies have confirmed that abnormal autophagy can cause abnormalities in the complex and highly ordered sperm cell differentiation process, such as acrosome biogenesis and sperm differentiation defects [28,29], decreased serum testosterone levels [30], and SC apoptosis and BTB damage [26,31]. The phosphatidylinositol 3kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway is a target of oxidative stress [32].…”

Section: Introductionmentioning

confidence: 99%

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Autophagy Induced by ROS Aggravates Testis Oxidative Damage in Diabetes via Breaking the Feedforward Loop Linking p62 and Nrf2

Tian

Song

et al. 2020

Oxidative Medicine and Cellular Longevity

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Testicular dysfunction due to hyperglycemia is the main cause of infertility in diabetic men. Over the years, in order to solve this growing problem, a lot of research has been done and a variety of treatments have been created, but so far, there is no safe, effective, and practical method to prevent male infertility caused by diabetes. In this review, we emphasize the male infertility mechanism caused by diabetes from the effects of oxidative stress and autophagy on the function of testes via the PI3K/Akt/mTOR signaling pathway, and we highlight that oxidative stress-induced autophagy breaks the feedforward loop linking Nrf2 and p62 and promotes oxidative damage in diabetic testes.

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Section: The Role Of Autophagy In Male Testicular Functionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Autophagy Induced by ROS Aggravates Testis Oxidative Damage in Diabetes via Breaking the Feedforward Loop Linking p62 and Nrf2

Tian

Song

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Adrenomedullin restored the steroidogenic enzyme expression, including StAR, CYP11A1, 3β‐HSD, and CYP17A1, and testosterone production in LPS‐induced Leydig cells via activation of the mTOR signaling pathway (Li et al, 2019). Nicotine decreased testosterone synthesis via inhibition of the mTOR signaling pathway in Leydig cells (Zhao et al, 2018). Therefore, we wanted to know whether ERO1α effects on testosterone secretory via regulation of the PI3K/AKT/mTOR signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

ERO1α promotes testosterone secretion in hCG‐stimulated mouse Leydig cells via activation of the PI3K/AKT/mTOR signaling pathway

Chen

Wang

Liu

et al. 2020

Journal Cellular Physiology

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ER oxidoreduclin 1α (ERO1α) is an oxidase, participating in formation of secretory and membrane proteins. However, the other physiological functions ERO1α is not well known. We found that ERO1α is high in the Leydig cells of the testis. Therefore, the purposes of the current study are to explore the role of ERO1α and the possible mechanisms in regulating cell proliferation, apoptosis, and testosterone secretion of Leydig cells. ERO1α was mainly localized in Leydig cells in the adult mice testes by immunofluorescence staining. Western blot analysis showed that ERO1α was higher in Leydig cells than that in the seminiferous tubules. The effect of ERO1α on cell proliferation, apoptosis, and testosterone secretion was detected by transducing ERO1α overexpression and knockdown lentiviruses into cultured primary Leydig cells (PLCs) together with hCG exposure. Flow cytometry analysis showed that ERO1α promoted cell proliferation by increasing cell distribution at the S phase and decreasing that at the G0/G1 phase. Western bolt analysis showed that ERO1α increased CDK2 and CDK6 expression. Cell apoptosis determination found that ERO1α inhibited PLC apoptosis. Western bolt analysis showed that ERO1α increased the ratio of BCL‐2/BAX, and decreased BAD and Caspase‐3 expression. Enzyme‐linked immunosorbent assay analysis demonstrated that ERO1α enhanced testosterone secretion. Western bolt analysis found that ERO1α increased StAR, 3β‐HSD, and CYP17A1 expression. Furthermore, ERO1α could activate the PI3K/AKT/mTOR signaling pathway. In summary, these results suggest that ERO1α might play proliferation promotion and antiapoptotic roles and enhance testosterone secretion in PLC, at least partly, via activation of the PI3K/AKT/mTOR signaling pathway.

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“…Nicotine and its metabolite cotinine can also disrupt spermatozoa parameters in a dose-dependent manner ( 58 ). In an in vitro study ( 59 ) nicotine reduced the number of TM3 Leydig cells, most likely through autophagy, and, consequently, testosterone synthesis. In vivo nicotine decreased testosterone levels in serum and impaired the function of other sex hormones (FSH, LH and prolactin) in albino rats ( 60 ).…”

Section: Smokingmentioning

confidence: 99%

“…Several other studies reported similar findings for drinking and abnormal semen parameters, especially morphology, but in combination with smoking ( 65 , 66 , 67 ). Smoking and obesity are confounding factors that often come in combination with moderate to heavy alcohol consumption ( 59 ) and make alcohol effects impossible to separate unless the confounding factors are excluded. One such study with non-smoking chronic alcoholics ( 68 ) reported higher serum FSH and LH and lower testosterone levels and semen quality.…”

Section: Alcoholmentioning

confidence: 99%

Environmental and occupational exposures associated with male infertility

Marić

Fučić

Aghayanian

2021

Archives of Industrial Hygiene and Toxicology

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The upsurge in male infertility over the last two decades, possibly due to environmental exposure, has raised significant interest, particularly boosted by reports from fertility clinics, which showed that chronic diseases and hereditary or other medical conditions might only partially explain current incidence of male infertility. Both environmental and occupational settings may have a significant role in exposure to complex mixtures of endocrine disruptors (ED), which play a major role in fertility disorders. The aim of this review is to give an insight into the current knowledge on exposure settings which may be associated with male infertility. Our study relied on a systematic search of PubMed, Scopus, and Web of Science for articles published between January 2000 and September 2020. It showed that some well documented factors associated with male infertility include smoking, and physiological disturbances or chronic diseases such as obesity and diabetes, which in turn, may also reflect lifestyle choices and environmental exposures, especially to EDs such as phthalates, bisphenols, pesticides, and flame retardants. However, the number of studies on the aetiology of male infertility is still too low in comparison with the size of affected population. Occupational health follow-ups and medical surveillance do not collect any data on male infertility, even though ED chemicals are part of many technological processes.

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Nicotine induced autophagy of Leydig cells rather than apoptosis is the major reason of the decrease of serum testosterone

Cited by 41 publications

References 38 publications

Autophagy Induced by ROS Aggravates Testis Oxidative Damage in Diabetes via Breaking the Feedforward Loop Linking p62 and Nrf2

Autophagy Induced by ROS Aggravates Testis Oxidative Damage in Diabetes via Breaking the Feedforward Loop Linking p62 and Nrf2

ERO1α promotes testosterone secretion in hCG‐stimulated mouse Leydig cells via activation of the PI3K/AKT/mTOR signaling pathway

Environmental and occupational exposures associated with male infertility

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