MDMA (ecstasy) delays pubertal development and alters sperm quality after developmental exposure in the rat

Barenys, Marta; Gómez‐Catalán, Jesús; Camps, Lydia; Teixidó, Elisabet; Lapuente, Joaquín de; Gonzalez-Linares, Javier; Serret, J.; Borràs, Miquel; Rodamilans, M.; Llobet, Juan M.

doi:10.1016/j.toxlet.2010.05.009

Cited by 19 publications

(12 citation statements)

References 52 publications

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“…Although there is a lack of data on the effect of paternal codeine exposure on offsprings, previous studies on nicotine revealed reduced average weight of progenies following nicotine exposure [59]. This is in dissonance with studies on 3,4-methylenedioxymethamphetamine (ecstasy) [60]. The present study revealed that codeine does not only trigger oxido-inflammatory damage to the gonads and sperm; it also exerts a negative effect on the quality of offsprings produced likely via epigenetic modification.…”

Section: Discussionsupporting

confidence: 65%

In vivo exposure to codeine induces reproductive toxicity: role of HER2 and p53/Bcl-2 signaling pathway

Ajayi

Akhigbe

2020

Heliyon

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Several studies have implicated codeine use in the aetiopathogenesis of male infertility. The purpose of this study was to investigate the role of HER2, Ki67, oestrogen and p53/Bcl-2 signaling pathways and the possible outcome of codeine cessation on codeine-induced reproductive toxicity. Thirty adult male Wistar rats of comparable ages and weights were randomly allocated into 5 groups. The control animals received distilled water per os (p.o), while animals in the low-dose (LDC) and high dose (HDC) codeine-treated groups received 2 and 5 mg/kg/day of codeine respectively p.o for 6 weeks. The animals in the low-dose codeine recovery (LDC-R) and high-dose codeine recovery (HDC-R) groups received treatment as LDC and HDC respectively followed by another drug-free six weeks, recovery period. Cessation of codeine exposure led to a partial reversal of codeine-induced poor sperm quality, reduced litter size and weight, increased oxidative testicular injury, testicular apoptosis, and testicular DNA damage caused by codeine administration. Codeine-induced gonado-spermotoxicity was associated with a reduction of circulatory testosterone, suppression of testicular HER2, Ki67, and Bcl-2 expression, down-regulation of oestrogen signaling, and upregulation of testicular caspase 3 activities and p53 signaling pathway. Conclusion: Upregulation of oestrogen signaling associated with enhanced testicular HER2 and Ki67 expression during the recovery period is seemingly beneficial in protecting against codeine-related testicular injury and infertility.

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Section: Discussionsupporting

confidence: 65%

In vivo exposure to codeine induces reproductive toxicity: role of HER2 and p53/Bcl-2 signaling pathway

Ajayi

Akhigbe

2020

Heliyon

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“…More recently, increased oxidative stress has been observed in mice following chronic administration of cocaine [ 98 ], suggesting a possible mechanism for testicular damage. Similar findings have been reported for Ecstasy and opioids: Barenys et al described significantly decreased sperm concentration and motility, together with increased rates of DNA damage and tubular degeneration, in rats treated with varying dosages of MDMA [ 99 ], and similar findings have been described in mice treated with either tramadol [ 100 ] or morphine [ 101 ].…”

Section: Introductionsupporting

confidence: 79%

Smoke, alcohol and drug addiction and male fertility

Sansone

Dato

Angelis

et al. 2018

Reprod Biol Endocrinol

208

113

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In recent decades, the decline in human fertility has become increasingly more worrying: while therapeutic interventions might help, they are vexing for the couple and often burdened with high failure rates and costs. Prevention is the most successful approach to fertility disorders in males and females alike. We performed a literature review on three of the most common unhealthy habits – tobacco, alcohol and drug addiction – and their reported effects on male fertility. Tobacco smoking is remarkably common in most first-world countries; despite a progressive decline in the US, recent reports suggest a prevalence of more than 30% in subjects of reproductive age – a disturbing perspective, given the well-known ill-effects on reproductive and sexual function as well as general health. Alcohol consumption is often considered socially acceptable, but its negative effects on gonadal function have been consistently reported in the last 30 years. Several studies have reported a variety of negative effects on male fertility following drug abuse – a worrying phenomenon, as illicit drug consumption is on the rise, most notably in younger subjects. While evidence in these regards is still far from solid, mostly as a result of several confounding factors, it is safe to assume that cessation of tobacco smoking, alcohol consumption and recreational drug addiction might represent the best course of action for any couple trying to achieve pregnancy.

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“…A common limitation of these rat in vivo studies is the low number of dose-response studies that investigate more than two doses. Only five papers include three dose groups of MDMA plus the control to support the evaluation of dose-response relationships (Barenys et al, 2010;Broening et al, 2001Broening et al, , 1994Dzietko et al, 2010;Vorhees et al, 2009Vorhees et al, , 2004. However, due to the overall low number of publications on the topic, single or two dose group studies were also considered in this review.…”

Section: Resultsmentioning

confidence: 99%

Developmental neurotoxicity of MDMA. A systematic literature review summarized in a putative adverse outcome pathway

et al. 2020

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The increasing use of illegal drugs by pregnant women causes a public health concern because it is associated with health risks for mothers and their developing children. One of such drugs is MDMA (3,4-methylenedioxymethamphetamine) or ecstasy due to its high consumption in relevant age and sex groups and its adverse effects on human and rodent developing brains. To thoroughly review the current knowledge on the developmentally neurotoxic potential of MDMA we systematically collected and summarized articles investigating developmental neurotoxicity (DNT) of MDMA in humans and animals in in vivo and in vitro. In addition, we summarized the findings in a putative adverse outcome pathway (AOP). From an initial 299 articles retrieved from the bibliographic databases Web of Science, PubMed and DART, we selected 39 articles according to inclusion/exclusion criteria for data collection after title/abstract and full text screening. Of these 3 where epidemiological studies, 34 where in vivo studies in mice and rats and 2 were in vitro studies. The three epidemiological studies reported from the same longitudinal study and suggested that MDMA exposure during pregnancy impairs neuromotor function in infants. In rat, postnatal exposure towards MDMA also caused locomotor deficits as well as impaired spatial learning that might be associated with decreased serotonin levels in the hippocampus. In vitro MDMA caused cytotoxicity at high concentrations and effects on the serotonergic and neuritogenic alterations at lower concentrations which are in line with some of the in vivo alterations observed. Considering the adverse outcomes of developmental MDMA described in humans and in rodents we summarized the first putative AOP on developmental compound exposure leading to impaired neuromotor function in children. For generation of this AOP, MDMA exposure was taken as a model compound. In addition, we hypothesized a second AOP involving developmental disturbance of the dopaminergic system. However, further in vitro mechanistic studies are needed to understand the molecular initiating event(s) (MIE) triggering the downstream cascades and obtain consistent evidences causally linking the adverse outcome to effects at the cellular, organ and organism level.

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MDMA (ecstasy) delays pubertal development and alters sperm quality after developmental exposure in the rat

Cited by 19 publications

References 52 publications

In vivo exposure to codeine induces reproductive toxicity: role of HER2 and p53/Bcl-2 signaling pathway

In vivo exposure to codeine induces reproductive toxicity: role of HER2 and p53/Bcl-2 signaling pathway

Smoke, alcohol and drug addiction and male fertility

Developmental neurotoxicity of MDMA. A systematic literature review summarized in a putative adverse outcome pathway

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