Dietary biotin supplementation increases proliferation pathways in mice testes without affecting serum follicle-stimulating hormone levels and stem cell factor expression

• Published in: Toxicology and applied pharmacology Vol. 433; p. 115774
• Main Authors: Salazar-Anzures, Tonatiuh, Pastén-Hidalgo, Karina, Sicilia-Argumedo, Gloria, Riverón-Negrete, Leticia, Hernández-Vázquez, Alain de Jesús, Fernanadez-Mejia, Cristina
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.12.2021
• Subjects: AKT; Animals; Biotin; Biotin - toxicity; C-Kit; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Proliferation - drug effects; Cyclins; Dietary Supplements - toxicity; ERK; Follicle Stimulating Hormone - blood; Male; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases - metabolism; Phosphorylation; Proliferation; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-kit - genetics; Proto-Oncogene Proteins c-kit - metabolism; Signal Transduction; Sp1 Transcription Factor - genetics; Sp1 Transcription Factor - metabolism; Sp3 Transcription Factor - genetics; Sp3 Transcription Factor - metabolism; Spermatogonia - drug effects; Spermatogonia - metabolism; Spermatogonia - pathology; Stem Cell Factor - metabolism; Testis - drug effects; Testis - metabolism; Testis - pathology; Ccna2; Ccne1; c-kit-Receptor; SE; ERK1; ERK2; p16; Sp1; Sp3; E2F; FSH; pAKTThr308; pAKTSer473; Ccnd3; C-Kit; AKT; Biotin; Proliferation; p21; Cyclins; Cdk4; Tuba1α; Cdk2; SCF; pERK1/2Tyr204; GAPDH; ERK
• ISSN: 0041-008X; 1096-0333; 1096-0333
• DOI: 10.1016/j.taap.2021.115774

Supplements containing pharmacological concentrations of biotin are commercially available. The mechanisms by which biotin at pharmacological concentrations exerts its action have been the subject of multiple investigations, particularly for biotin's medicinal potential and wide use for cosmetic purposes. Several studies have reported that biotin supplementation increases cell proliferation; however, the mechanisms involved in this effect have not yet been characterized. In a previous study, we found that a biotin-supplemented diet increased spermatogonia proliferation. The present study was focused on investigating the molecular mechanisms involved in biotin-induced testis cell proliferation. Male BALB/cAnNHsd mice were fed a control or a biotin-supplemented diet (1.76 or 97.7 mg biotin/kg diet) for eight weeks. Compared with the control group, the biotin-supplemented mice presented augmented protein abundance of the c-kit-receptor and pERK1/2Tyr204 and pAKTSer473, the active forms of ERK/AKT proliferation signaling pathways. No changes were observed in the testis expression of the stem cell factor and in the serum levels of the follicle-stimulating hormone. Analysis of mRNA abundance found an increase in cyclins Ccnd3, Ccne1, Ccna2; Kinases Cdk4, Cdk2; and E2F; and Sp1 & Sp3 transcription factors. Decreased expression of cyclin-dependent kinase inhibitor 1a (p21) was observed but not of Cdkn2a inhibitor (p16). The results of the present study identifies, for the first time, the mechanisms associated with biotin supplementation-induced cell proliferation, which raises concerns about the effects of biotin on male reproductive health because of its capacity to cause hyperplasia, especially because this vitamin is available in large amounts without regulation. •Biotin supplementation effects on testis cell proliferation are independent of FSH.•Biotin supplementation increases the expression of several cell cycle transcripts.•Biotin supplementation increases the expression of Sp1 and Sp3 transcripts.•Spermatogonia expression of c-kit receptor increases due to biotin supplementation.•Biotin supplementation enhances the activation of MAPK and AKT signaling pathways.