Contractile Effects of Serotonin (5-HT) in the Rat Cauda Epididymis: Expression and Functional Characterization of 5-HT Receptors

Mueller, André N.; Kiguti, Luiz Ricardo de Almeida; Silva, Erick J. R.; Pupo, André S.

doi:10.1124/jpet.118.254110

Cited by 8 publications

(5 citation statements)

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“…(2007), 47 the caput portion of the epididymis, in rats, has a local serotonergic system that controls the expression of enzymes for the biosynthesis of serotonin (5‐Hydroxytruptamine – 5HT), besides some receptors for SSRI that are involved in muscular contractions in the cauda portion. This indicates that serotonergic transmission participates of the muscular contraction of the epididymal cauda during the sperm transit period, which is a fundamental event for the fertility 71 . In fact, escitalopram is used to treat premature ejaculation, so, the impact of changes in epididymal transit observed here, related to the escitalopram treatment, deserves further investigation.…”

Section: Discussionmentioning

confidence: 70%

“…This indicates that serotonergic transmission participates of the muscular contraction of the epididymal cauda during the sperm transit period, which is a fundamental event for the fertility. 71 In fact, escitalopram is used to treat premature ejaculation, so, the impact of changes in epididymal transit observed here, related to the escitalopram treatment, deserves further investigation.…”

Section: Discussionmentioning

confidence: 79%

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Effects of escitalopram treatment and chronic mild stress induced from peripuberty on spermatic parameters of adult rats

et al. 2022

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Background The prevalence of depression in adolescents has significantly increased worldwide. Escitalopram is a selective serotonin reuptake inhibitor approved for treatment of psychiatric disorders in children and adolescents by the Food and Drugs Administration. Aims This study aimed to evaluate the sperm parameters of adult rats exposed to chronic mild stress (CMS), from peripuberty to adulthood, treated or not with escitalopram. Materials and methods Sixty‐two male rats were distributed into four groups: S ‐ submitted to CMS; E ‐ Escitalopram (10 mg / kg, via gavage); ES ‐ CMS + ES; SC ‐ Sham control. The induced depression protocol consisted of the exposure of the animals to nine different stressors (one stressor/day), randomly for 8 weeks, from peripuberty (41 days postpartum, dpp) to adulthood (97 dpp). The escitalopram treatment period started at 70 dpp and lasted 4 weeks. The euthanasia was performed for biological material collection at 114 dpp. Morphometric, biometric, sperm parameters, oxidative stress analyses, and corticosterone dosage were carried out. Results There was a reduction of the sperm daily production and sperm concentration in the epididymis of rats treated and/or submitted to CMS. These groups (E, S, ES) also showed reduction of the mitochondrial activity; acrosome integrity; sperm chromatin compaction; sperm motility and vitality, besides an increased frequency of morphologically abnormal sperm. The sperm transit time through the epididymis was significantly higher in the escitalopram‐treated rats (E, ES). No differences were observed regarding the sperm DNA fragmentation. The lipid peroxidation was significantly increased at the epididymal (E, S, and ES group) and testicular levels (S group). Conclusion The CMS with or without escitalopram treatment altered the oxidative status in sperm and male organs, worsening the qualitative and quantitative sperm parameters, which can probably compromise the male fertility.

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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 79%

Effects of escitalopram treatment and chronic mild stress induced from peripuberty on spermatic parameters of adult rats

et al. 2022

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“…В нашем исследовании было зафиксировано незначительное уменьшение объёма эякулята и концентрации сперматозоидов. Данный изменения могут быть обусловлены как нарушением эвакуаторной функции, так и секреторной активности добавочных половых желез и яичек на фоне приёма препарата [18,19,20] Наши наблюдения показали, что негативные изменения со стороны сперматогенеза после приёма флуоксетина имеют обратимый характер. Через 3 месяца после отмены препарата показатели эякулята улучшились и практически вернулись к исходным значениям.…”

Section: Discussionunclassified

Selective serotonin reuptake inhibitors and spermatogenesis

et al. 2021

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Introduction. According to the WHO data, depression is a common disease among women and men of reproductive age. One line of the correction of depressive disorders is selective serotonin reuptake inhibitors (SSRIs). The ingestions have shown that using SSRIs harms sperm quality. The literature date of evaluation of male fertility after discontinuation of antidepressants is quite limited.Purpose of the study. To evaluate the influence of Fluoxetine intake on semen parameters, sperm DNA fragmentation and hormonal status.Materials and methods. Twenty-five men (mean age - 35.2 ± 4.5 yo) with depression were included in the study. Fluoxetine (20 mg per day) was prescribed to all the patients for 12 wk. Semen parameters, sperm DNA fragmentation, sex hormones levels were measured before-after treatment and 3 mo behind discontinuation.Results. After 12 weeks of the treatment the mean semen volume decreased from 3.1 ± 0.7 to 2.9 ± 0.7 ml (p = 0.638), sperm concentration - from 39.4 ± 18.5 to 34.3 ± 16.8 mln/ml (p = 0.384), sperm motility decreased from 41.7 ± 7.6 to 35.5 ± 7.8% (p < 0.05), the mean percent of normal morphology form - from с 12.7 ± 2.8 to 10.7 ± 2.2% (p < 0.001). Sperm DNA fragmentation increased 16.2 ± 4.9 to 22.2 ± 4.3% (p < 0.001). The mean semen volume, sperm concentration, motility, percentage of normal morphology increased and reverted to the normal levels after 3 mounts of drug discontinuation. Sperm DNA fragmentation index decreased, and it had the values less than before the treatment that positively correlated with the reduction of depression's symptoms. It was not significant dynamics in hormonal parameters before and after the therapy.Conclusion. Using fluoxetine has a reversible negative effect on male fertility. It is important to inform the patients about the temporary side effects of SSRIs in fatherhood planning cases.

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“…The current literature shows that 5‐HT released from the synapse acts on postsynaptic neuronal receptors and mainly inhibits ejaculation. On the other hand, the released 5‐HT can be reuptaked by the 5‐hydroxytryptamine transporter (5‐HTT), terminating its biological activity 5 . Therefore, selective serotonin reuptake inhibitors (SSRIs) have been successfully used to treat PE, which can bind to 5‐HTT and prevent the reuptake of 5‐HT into the presynaptic axon terminal, increasing the synaptic levels of 5‐HT and delaying ejaculation 2,6 .…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, the released 5-HT can be reuptaked by the 5-hydroxytryptamine transporter (5-HTT), terminating its biological activity. 5 Therefore, selective serotonin reuptake inhibitors (SSRIs)…”

Section: Introductionmentioning

confidence: 99%

Vital function of DRD4 in dapoxetine medicated premature ejaculation treatment

et al. 2023

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Background Recently, dapoxetine has been widely accepted to treat premature ejaculation by fast‐inhibiting 5‐hydroxytryptamine reuptake. However, dapoxetine is not suitable for all premature ejaculation patients in clinical treatment. We need to investigate and reveal the mechanism deeply to solve this problem. Objectives To investigate and reveal the function of dopamine D4 receptor in dapoxetine medicated premature ejaculation treatment. Materials and methods A rat model was used to screen rapid ejaculators. The molecular mechanisms of histone serotonylation‐mediated regulation of dopamine D4 receptor were demonstrated by chromatin immunoprecipitation, DNA pull‐down, mass spectrometry analysis, and coimmunoprecipitation experiments. The biological function of dopamine D4 receptor was investigated through in vivo experiments by intrathecal injection of shDRD4 to knockdown dopamine D4 receptor. Results In this study, we found that dapoxetine increased expression of 5‐hydroxytryptamine and dopamine D4 receptor. We demonstrated that dapoxetine increased levels of 5‐hydroxytryptamine, which promoted histone serotonylation (H3K4me3Q5ser) and transcription factor myeloid zinc‐finger 1 complex binding on the dopamine D4 receptor promoter, upregulated the expression of dopamine D4 receptor and thus delayed ejaculation. Discussion In this study, we demonstrated that dapoxetine increased the levels of 5‐hydroxytryptamine, which promoted histone serotonylation and myeloid zinc‐finger 1 complex binding to the dopamine D4 receptor promoter and upregulated the expression of dopamine D4 receptor, thus delaying ejaculation. Conclusion It is a novel mechanism that dapoxetine take effect of premature ejaculation treatment through upregulating the dopamine D4 receptor, which indicated that upregulated dopamine D4 receptor would enhance the dapoxetine effect in premature ejaculation treatment. This may lead to the development of novel therapeutic interventions for premature ejaculation.

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Contractile Effects of Serotonin (5-HT) in the Rat Cauda Epididymis: Expression and Functional Characterization of 5-HT Receptors

Cited by 8 publications

References 58 publications

Effects of escitalopram treatment and chronic mild stress induced from peripuberty on spermatic parameters of adult rats

Effects of escitalopram treatment and chronic mild stress induced from peripuberty on spermatic parameters of adult rats

Selective serotonin reuptake inhibitors and spermatogenesis

Vital function of DRD4 in dapoxetine medicated premature ejaculation treatment

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