Fluoxetine-induced androgenic failure impairs the seminiferous tubules integrity and increases ubiquitin carboxyl-terminal hydrolase L1 (UCHL1): Possible androgenic control of UCHL1 in germ cell death?

Câmara, Marina Luiza; Almeida, Talita Bonato de; Santi, Fabiane de; Rodrigues, Beatriz M.; Cerri, Paulo Sérgio; Beltrame, Flávia Luciana; Sasso-Cerri, Estela

doi:10.1016/j.biopha.2018.10.034

Cited by 22 publications

(26 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is known that androgens are essential for the seminiferous epithelium and spermatogenic process (Smith and Walker 2014 ). Several studies have demonstrated a direct correlation between low serum T levels (due to impaired steroidogenesis and/or LC) and damage to the seminiferous epithelium, including SC integrity (Beltrame et al 2019 ; Câmara et al 2019 ). In the present study, the testes of animals from DIAG showed low AR protein levels as well as weak AR immunolabelling either in SC or LC in comparison with CG.…”

Section: Discussionmentioning

confidence: 99%

Impaired macrophages and failure of steroidogenesis and spermatogenesis in rat testes with cytokines deficiency induced by diacerein

Oliveira

Cerri

Sasso-Cerri

2021

Histochem Cell Biol

Self Cite

View full text Add to dashboard Cite

The role of cytokines in testicular function under normal conditions has not been completely understood. Here, we evaluated testicular macrophages (TM), steroidogenesis by Leydig cells (LC) and seminiferous tubules integrity in cytokines-deficient rat testes induced by diacerein, an anti-inflammatory drug that inhibits interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α). Male rats received daily 100 mg/kg of diacerein (DIAG; n = 8) or saline (CG; n = 8) for 30 days. Serum testosterone (T) levels were measured and the seminiferous tubule (ST) area, epithelial area (EA), frequency of damaged ST and number of Sertoli cells (SC) were evaluated. TUNEL method and immunoreactions for detection of pro-IL-1β, TNF-α, steroidogenic acute regulatory protein (StAR), 17β-hydroxysteroid dehydrogenase (17β-HSD), androgen receptor (AR) and scavenger receptor for hemoglobin-haptoglobin complexes (CD163), a TM marker, were performed. Testicular AR, 17β-HSD and IL-1β levels were detected by Western blot. Data were submitted to Student t test ( p ≤ 0.05). In DIAG, T and testicular AR, 17β-HSD and IL-1β levels decreased significantly ( p < 0.05). The number of TUNEL-positive interstitial cells increased and LC showed weak StAR, 17β-HSD and AR immunoexpression in association with reduced IL-1β immunoexpression and number of CD163-positive TM in the interstitial tissue from diacerein-treated rats. Numerous damaged ST were found in DIAG, and reduction in the EA were associated with germ cells death. Moreover, the number of SC reduced and weak AR and TNF-α immunoexpression was observed in SC and germ cells, respectively. The cytokines deficiency induced by diacerein impairs TM, LC and spermatogenesis, and points to a role of IL-1β in steroidogenesis under normal conditions. In the ST, the weak AR and TNF-α immunoexpression in SC and germ cells, respectively, reinforces the idea that TNF-α plays a role in the SC androgenic control.

show abstract

Section: Discussionmentioning

confidence: 99%

Impaired macrophages and failure of steroidogenesis and spermatogenesis in rat testes with cytokines deficiency induced by diacerein

Oliveira

Cerri

Sasso-Cerri

2021

Histochem Cell Biol

Self Cite

View full text Add to dashboard Cite

show abstract

“…The present study demonstrated that fluoxetine exerted a pronounced DNA damage in testicular tissues (Group 2) compared to the negative control (Group 1) rats, as represented by comet scores in (Table 1) and (Figure 1). Testicular or germ cells are important target in reproductive toxicology, which seems to be an easier and logical choice for DNA damage assessment and reproductive genotoxicity research by comet assay (35) ; where, a recent study by Câmara et al (2019) (36) demonstrated that the effect of short-term treatment with fluoxetine on the adult rat testes caused a significant increase of ubiquitin carboxylterminal hydrolase L1 (UCHL1) isoenzyme in the damaged seminiferous tubules associated with high incidence of cell death, since the ubiquitination minimizes DNA damage when spermatogonia are exposed to stress. The authors described that such isoenzyme seems to control spermatogenesis, as well as it involved in the molecular regulation of germ cells apoptosis.…”

Section: Comet Assay In the Hepatic And Testicular Tissue Homogenatementioning

confidence: 99%

Assessment the Genotoxic Potential of Fluoxetine and Amitriptyline at Maximum Therapeutic Doses for Four-Week Treatment in Experimental Male Rats

Al-Obaidi¹,

Al-Shawi²

2021

IJPS

View full text Add to dashboard Cite

At any moment, the continuous usage of medications can accompanied by DNA damage and the accumulation of such damages can cause serious consequences. Antidepressants are long-term used drugs and the incidence of their genotoxic impacts cannot be excluded. Therefore, this work was designed to investigate the possible genotoxic effects of the commonly used antidepressants (fluoxetine and amitriptyline) in adult male rats. Detection of DNA damage in individual cells was assessed by comet and micronucleus assays in three different cell populations i.e. liver, testis and bone marrow tissues of 24 swiss albino adult male rats. The animals were randomly allocated into three groups of 8 rats each: Group I - rats orally-administered distilled water via gavage tube for four weeks as a negative control. Group II - rats orally-treated with fluoxetine hydrochloride solution (7.2mg/kg/day) via gavage tube for four weeks. Group III - rats orally-treated with amitriptyline hydrochloride solution (27mg/kg/day) via gavage tube for four weeks. The results showed that both drugs (Group II and Group III) induced the same extent of DNA damage, as evidenced by a significantly higher DNA fragmentation in liver and testis tissues with increased frequencies of micronuclei formation in bone marrow tissues as compared with the negative control (Group I). These findings indicates that both Fluoxetine and Amitriptyline have genotoxic potentials and can induce the same extent of cytogenetic damage in rats. Special precautions and medical supervision should be taken in consideration with their uses.

show abstract

“…Decreased level of androgen leads to increased level of UCHL1 in spermatocytes, which will lead to deubiquitination of the pro-apoptotic factor p53. Deubiquitination of p53 triggers germ cell death ( 104 ). In addition, phagocytic clearance of apoptotic germ cells by SCs is vital for meiosis because phagocytosis of dying GCs provides lipid sources for SCs which will provide ATP for GCs development.…”

Section: Androgen Receptor Signaling Pathway In Sertoli Cells Can Reg...mentioning

confidence: 99%

What Does Androgen Receptor Signaling Pathway in Sertoli Cells During Normal Spermatogenesis Tell Us?

Wang

Yang

2022

Front. Endocrinol.

View full text Add to dashboard Cite

Androgen receptor signaling pathway is necessary to complete spermatogenesis in testes. Difference between androgen binding location in Sertoli cell classifies androgen receptor signaling pathway into classical signaling pathway and non-classical signaling pathway. As the only somatic cell type in seminiferous tubule, Sertoli cells are under androgen receptor signaling pathway regulation via androgen receptor located in cytoplasm and plasma membrane. Androgen receptor signaling pathway is able to regulate biological processes in Sertoli cells as well as germ cells surrounded between Sertoli cells. Our review will summarize the major discoveries of androgen receptor signaling pathway in Sertoli cells and the paracrine action on germ cells. Androgen receptor signaling pathway regulates Sertoli cell proliferation and maturation, as well as maintain the integrity of blood-testis barrier formed between Sertoli cells. Also, Spermatogonia stem cells achieve a balance between self-renewal and differentiation under androgen receptor signaling regulation. Meiotic and post-meiotic processes including Sertoli cell - Spermatid attachment and Spermatid development are guaranteed by androgen receptor signaling until the final sperm release. This review also includes one disease related to androgen receptor signaling dysfunction named as androgen insensitivity syndrome. As a step further ahead, this review may be conducive to develop therapies which can cure impaired androgen receptor signaling in Sertoli cells.

show abstract

Fluoxetine-induced androgenic failure impairs the seminiferous tubules integrity and increases ubiquitin carboxyl-terminal hydrolase L1 (UCHL1): Possible androgenic control of UCHL1 in germ cell death?

Cited by 22 publications

References 69 publications

Impaired macrophages and failure of steroidogenesis and spermatogenesis in rat testes with cytokines deficiency induced by diacerein

Impaired macrophages and failure of steroidogenesis and spermatogenesis in rat testes with cytokines deficiency induced by diacerein

Assessment the Genotoxic Potential of Fluoxetine and Amitriptyline at Maximum Therapeutic Doses for Four-Week Treatment in Experimental Male Rats

What Does Androgen Receptor Signaling Pathway in Sertoli Cells During Normal Spermatogenesis Tell Us?

Contact Info

Product

Resources

About