GABAergic Alterations in the Rat Testis after Methamphetamine Exposure

Kaewman, Paweena; Nudmamud-Thanoi, Sutisa; Thanoi, Samur

doi:10.7150/ijms.27609

Cited by 19 publications

(27 citation statements)

References 17 publications

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“…Regarding spermatogenesis, amphetamines induce apoptosis in murine testicular germ cells [114]. Oxidative stress, overproduction of serotonin and GABA, thermic rise, and decreased expression of progesterone and estradiol receptors in testis have been called into question in the pathogenesis of testicular damage [111,116,119].…”

Section: Discussionmentioning

confidence: 99%

“…An increase in testicular GABA concentration has also been reported in methamphetamine treated rats [111]. Since GABA is involved in the proliferation of Leydig cells and testosterone production, Authors hypothesized that the increase in GABA concentration could represent a compensatory response to the detrimental effects of methamphetamine on Leydig cells [111].…”

Section: Effects On Testosterone Productionmentioning

confidence: 97%

“…Finally, increased GABA concentrations have been found in rat testicular tissue after methamphetamine administration. Since GABA activity can suppress the proliferation of spermatogonial stem cells, the increase in its concentration could lead to alteration of proliferation/apoptosis ratio [111].…”

Section: Effects On Spermatogenesismentioning

confidence: 99%

“…Inhibition of GnRH and LH in animal models [81,83] Reduced expression of LH receptor on testis in animal models [86] Reduced activity of testicular 3β-hydroxysteroid dehydrogenase in animal models [86] ↓ Induction of apoptosis [71] Cocaine ↔ Panhypopituitarism for pituitary infarction or inflammation (case reports) [96,97] ↓ Testicular vasoconstriction and ischemia [99] Induction of apoptosis [102] Pro-oxidant effect (reperfusion injury) [103] Amphetamines ↓ Decreased expression of GnRH mRNA [112] Activation of adenylate cyclase [106] Inhibition of 3b-hydroxysteroid dehydrogenase, P450c17, and 17-ketosteroid reductase [107] Reduced Ca 2 + influx [107] Increased testicular GABA concentration [111] ↓ Induction of apoptosis [114][115][116] Pro-oxidant effect [110] Testicular thermic damage [119] Increased testicular serotonin concentration [115] Increased testicular GABA concentration [111] Reduced testicular expression of progesterone and estrogen receptors [116] Opioids ↓ Inhibition of GnRH secretion [120,134] Hyperprolactinemia [120] ↓ Induction of apoptosis [128,140] Pro-oxidant effect [128][129][130][131][132][133][134][135][136][137][138]…”

Section: Substance Effect On Testosterone Hypothesized Mechanisms Effmentioning

confidence: 99%

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Substance Abuse and Male Hypogonadism

Duca

Aversa

Condorelli

et al. 2019

JCM

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Progressive deterioration of male reproductive function is occurring in Western countries. Environmental factors and unhealthy lifestyles have been implicated in the decline of testosterone levels and sperm production observed in the last fifty years. Among unhealthy lifestyles, substance and drug abuse is a recognized cause of possible alterations of steroidogenesis and spermatogenesis. Alcohol, opioids and anabolic-androgenic steroids are capable to reduce testosterone production in male interfering with testicular and/or hypothalamic-pituitary function. Other substances such as nicotine, cannabis, and amphetamines alter spermatogenesis inducing oxidative stress and subsequent apoptosis in testicular tissue. Substance and drug abuse is a potentially reversible cause of hypogonadism, defined as the failure of the testis to produce physiological concentrations of testosterone and/or a normal number of spermatozoa. The identification of the abuse is important because the withdrawal of substance intake can reverse the clinical syndrome. This review summarizes the most important clinical and experimental evidence on the effect of substance abuse on testosterone and sperm production.

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Section: Discussionmentioning

confidence: 99%

Section: Effects On Testosterone Productionmentioning

confidence: 97%

Section: Effects On Spermatogenesismentioning

confidence: 99%

Section: Substance Effect On Testosterone Hypothesized Mechanisms Effmentioning

confidence: 99%

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Substance Abuse and Male Hypogonadism

Duca

Aversa

Condorelli

et al. 2019

JCM

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“…To some extent, the exhaustion of energy and glucose metabolism might account for the aforementioned results. A recent study also showed that after METH exposure, the compensatory upregulation of gamma-aminobutyric acid (GABA), GABA-A receptors and GABA transporter 1 (GAT1) in rats testes tissues appeared [28], which might represent a homeostatic response to the adverse effects of METH exposure by inhibiting local mechanism and reducing energy consumption. Moreover, enzymes related to glycolysis, including HK1 and LDHC, might be broken down because of the reduction of GLUT1 and G-6-P according to the theoretical basis of enzyme catalysis [29].…”

Section: Discussionmentioning

confidence: 99%

Reduced Glycolysis Contributed to Inhibition of Testis Spermatogenesis in Rats After Chronic Methamphetamine Exposure

Shen

Chen

et al. 2019

Med Sci Monit

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Background Previous reports suggested that methamphetamine (METH) exposure could lead to inhibition of rat testis spermatogenesis. Glycolysis and glucose metabolism as well as oxidative stress have been implicated in testis spermatogenesis. Here we explored the underlying mechanism of local metabolism and glycolysis of testis after METH exposure. Material/Methods METH was intraperitoneally injected into rats with different doses and duration of METH exposure to establish short-term and chronic exposure models. The serum 8-hydroxy-2 deoxyguanosine (8-OHdG) level of rats was detected by enzyme-linked immunosorbent assay. Untargeted gas chromatography-mass spectrometry analysis was applied to identify differential metabolites and metabolic signature. The mRNA expression of hypoxia inducible factor 1α (HIF1α), glucose transporter 1 (GLUT1), hexokinase 1 (HK1) and lactate dehydrogenase C (LDHC) in rat testes were detected by polymerase chain reaction. Further, we determined the 4 proteins with western blotting and immunohistochemistry. Results Decreased testes index and sperm counts were showed in the chronic METH group. The metabolome revealed that the main differential metabolites impacted were associated with glycolysis and glucose metabolism. The mRNA and protein expression of GLUT1, HK1, and LDHC were reduced in the chronic METH group but elevated in the short-term METH group, whereas HIF1α was upregulated in the short-term METH group but remained at baseline in the chronic METH group. Conclusions Overall, glucose metabolism was regulated by HIF1α after short-term METH exposure. Reduced glycolysis in the testis led to impaired spermatogenesis after chronic METH exposure.

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