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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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?

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Camara, Marina L. [1] ; Almeida, Talita B. [1] ; de Santi, Fabiane [2] ; Rodrigues, Beatriz M. [1] ; Cerri, Paulo S. [1] ; Beltrame, Flavia L. [2] ; Sasso-Cerri, Estela [1]
Total Authors: 7
[1] Sao Paulo State Univ, Dept Morphol, Dent Sch, Araraquara - Brazil
[2] Univ Fed Sao Paulo, Dept Morphol & Genet, Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: BIOMEDICINE & PHARMACOTHERAPY; v. 109, p. 1126-1139, JAN 2019.
Web of Science Citations: 2

The selective serotonin reuptake inhibitor fluoxetine has been used for the treatment of depression. Although sexual disorders have been reported in male patients, few studies have demonstrated the fluoxetine effect on the reproductive histophysiology, and the target of this antidepressant in testes is unknown. We evaluated the impact of short-term treatment with fluoxetine on the adult rat testes, focusing on steroidogenesis by Leydig cells (LC) and androgen-dependent testicular parameters, including Sertoli cells (SC) and peritubular myoid cells (PMC). Since UCHL1 (ubiquitincarboxyl-terminal hydrolase L1) seems to control spermatogenesis, the immunoexpression of this hydrolase was also analyzed. Adult male rats received 20 mg/kg BW of fluoxetine (FG) or saline (CG) for eleven days. In historesin-embedded testis sections, the seminiferous tubule (ST) and epithelial (Ep) areas, and the LC nuclear diameter (LCnu) were measured. The number of abnormal ST, androgen-dependent ST, SC and PMC was quantified. Testicular beta-tubulin levels and peritubular actin immunofluorescence were evaluated. Serum testosterone levels (STL) and steroidogenesis by 17 beta-HSD6 immunofluorescence were analyzed, and either UCHL1-immunolabeled or TUNEL-positive germ cells were quantified. In FG, abnormal ST frequency increased whereas ST and Ep areas, androgen-dependent ST number, LCnu, 17 beta-HSD6 activity and STL reduced significantly. TUNEL-positive PMC and SC was related to decreased number of these cells and reduction in peritubular actin and beta-tubulin levels. In FG, uncommon UCHL1-immunoexpression was found in spermatocytes and spermatids, and the number of UCHL1-immunolabeled and TUNEL-positive germ cells increased in this group. These findings indicate that LC may be a fluoxetine target in testes, impairing PMC-SC integrity and disturbing spermatogenesis. The increase of UCHL1 in the damaged tubules associated with high incidence of cell death confirms that this hydrolase regulates germ cell death and may be controlled by androgens. The fertility in association with the androgenic status of patients treated with fluoxetine should be carefully evaluated. (AU)

FAPESP's process: 11/19132-9 - Effect of the antidepressant fluoxetin hydrochloride in the seminiferous tubules of adult rats
Grantee:Marina Luiza Câmara
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 13/04867-9 - Evaluation of morphometric and morphofunctional parameters in the testis of fluoxetine treated and vitamin B12 supplemented rats
Grantee:Talita Bonato de Almeida
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 12/23845-3 - Evaluation of Vitamin B12 effect on the mitotic and meiotic phases of spermatogenesis and in the sperm DNA of cimetidine-treated rats
Grantee:Estela Sasso Cerri
Support type: Regular Research Grants