| Full text | |
| Author(s): |
Beltrame, Flavia Luciana
;
Moyses, Thiago Henrique Pereira
;
Coelho, Monica Pereira
;
Steinvascher, Maria Clara Rossetto
;
de Oliveira, Salmo Azambuja
;
da Silva, Andre Acacio Souza
;
Cerri, Paulo Sergio
;
Sasso-Cerri, Estela
Total Authors: 8
|
| Document type: | Journal article |
| Source: | ANDROLOGY; v. N/A, p. 19-pg., 2023-09-07. |
| Abstract | |
BackgroundParoxetine, a selective serotonin reuptake inhibitor (SSRI) antidepressant, has caused male sexual dysfunction; however, the paroxetine mechanisms of action in testes are still unclear.ObjectivesParoxetine serotonergic effects in testes were evaluated, focusing on steroidogenesis and the correlation between macrophages population and possible TNF-& alpha;-derived oxidative stress. We also verified whether the changes are reversible following treatment interruption.Materials and methodsAdult rats received paroxetine (PG35 and PG65) or tap water (CG) for 35 days. PG65 was maintained without treatment for 30 more days. Intratesticular testosterone (IT), nitrite, and malondialdehyde concentrations were measured. To confirm serotonergic and estrogenic effects, Htr1b and Esr1 expressions were analyzed. The daily sperm production (DSP), frequency of abnormal seminiferous tubules (ST), SC number, ST area, and Leydig cells nuclear area (LCnu) were evaluated. TUNEL+ germ cells, M1 (CD68+), and M2 (Perls+) macrophages were quantified. 17 & beta;-HSD7, CYP19A1, NDRG2, oxytocin, TNF-& alpha;, and iNOS were evaluated by immunoreactions. Oxytocin and NDRG2 protein levels as well as Tnfa mRNA expression were also analyzed.ResultsThe Htr1b downregulation in testes confirmed the paroxetine serotonergic effect. The testicular sections showed abnormal ST frequency, ST atrophy and reduction of DSP, LCnu, SC number and Perls+ macrophages. TUNEL+ germ cells and LC were associated with strong NDRG2 immunoexpression. Paroxetine reduced IT levels and 17 & beta;-HSD7 immunoexpression in parallel to increased CYP19A1, oxytocin, TNF-& alpha; and iNOS. Esr1 and Tnfa overexpression and increased number of CD68+ macrophages were also observed together with high nitrite and malondialdehyde levels. Most parameters were not recovered in PG65.ConclusionsParoxetine serotonergic effect impairs LC steroidogenesis, via aromatization, increasing estrogen/testosterone ratio, which in turn upregulate NDRG2, promoting apoptosis, and impairing sperm production. Serotonin-estrogen pathways may be responsible for M2/M1 polarization, Tnfa upregulation, and induction of oxidative stress. The unrecovered testicular changes after treatment discontinuation are due to persistent paroxetine serotonin/estrogen effects. (AU) | |
| FAPESP's process: | 22/10560-2 - Immunological response of epididymis of K18-hACE2 transgenic mice infected with SARS-CoV-2, with emphasis on the clear cell |
| Grantee: | André Acácio Souza da Silva |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 21/07207-6 - Histopathological evaluation of testis, epididymis and submandibular gland of SARS-CoV-2-infected K18-hACE2 mice |
| Grantee: | Estela Sasso Cerri |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 17/19829-6 - EFFECT OF VENLAFAXINE ON THE MALE REPRODUCTIVE HISTOPHYSIOLOGY AND SPERM PARAMETERS OF ADULT RATS |
| Grantee: | Estela Sasso Cerri |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 21/09328-5 - Evaluation of immunological profile, spermatogenesis and steroidogenesis in SARS-CoV-2-infected K18-hACE2 mice |
| Grantee: | Salmo Azambuja de Oliveira |
| Support Opportunities: | Scholarships in Brazil - Doctorate |