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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?
Biomed Pharmacother. 2019 Jan; 109:1126-1139.BP

Abstract

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 β-tubulin levels and peritubular actin immunofluorescence were evaluated. Serum testosterone levels (STL) and steroidogenesis by 17β-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, 17β-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 β-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.

Authors+Show Affiliations

Dental School of São Paulo State University, Department of Morphology, Araraquara, Brazil.Dental School of São Paulo State University, Department of Morphology, Araraquara, Brazil.Federal University of São Paulo, Department of Morphology and Genetics, São Paulo, Brazil.Dental School of São Paulo State University, Department of Morphology, Araraquara, Brazil.Dental School of São Paulo State University, Department of Morphology, Araraquara, Brazil.Federal University of São Paulo, Department of Morphology and Genetics, São Paulo, Brazil.Dental School of São Paulo State University, Department of Morphology, Araraquara, Brazil. Electronic address: esasso@foar.unesp.br.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30551363

Citation

Câmara, Marina L., et al. "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?" Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 109, 2019, pp. 1126-1139.
Câmara ML, Almeida TB, de Santi F, et al. 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? Biomed Pharmacother. 2019;109:1126-1139.
Câmara, M. L., Almeida, T. B., de Santi, F., Rodrigues, B. M., Cerri, P. S., Beltrame, F. L., & Sasso-Cerri, E. (2019). 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? Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 109, 1126-1139. https://doi.org/10.1016/j.biopha.2018.10.034
Câmara ML, et al. 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. Biomed Pharmacother. 2019;109:1126-1139. PubMed PMID: 30551363.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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? AU - Câmara,Marina L, AU - Almeida,Talita B, AU - de Santi,Fabiane, AU - Rodrigues,Beatriz M, AU - Cerri,Paulo S, AU - Beltrame,Flávia L, AU - Sasso-Cerri,Estela, Y1 - 2018/11/06/ PY - 2018/08/16/received PY - 2018/09/28/revised PY - 2018/10/09/accepted PY - 2018/12/16/entrez PY - 2018/12/16/pubmed PY - 2019/3/29/medline KW - Peritubular myoid cell KW - SSRI KW - Sertoli cell KW - Spermatogenesis KW - Steroidogenesis KW - Ubiquitin hydrolase SP - 1126 EP - 1139 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed Pharmacother VL - 109 N2 - 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 β-tubulin levels and peritubular actin immunofluorescence were evaluated. Serum testosterone levels (STL) and steroidogenesis by 17β-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, 17β-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 β-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. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/30551363/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 L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(18)35636-1 DB - PRIME DP - Unbound Medicine ER -