Minocycline can improve the sperm parameters and regulates hormonal receptor expression in a varicocele-induced rat model

La minociclina puede mejorar los parámetros espermáticos y regular la expresión de receptores hormonales en un modelo de rata inducido por varicocele

Background: Varicocele, a common cause of male infertility, impairs reproductive function through oxidative stress and disruption of the hypothalamic-pituitary-gonadal (HPG) axis. Minocycline, a tetracycline antibiotic, possesses potent antioxidant and anti-apoptotic properties beyond its antimicrobial effects. This study aimed to evaluate the potential protective effects of minocycline on sperm parameters, hormonal levels, and the expression of key hormonal receptors and ion channels in a rat model of varicocele. Methods: Thirty-two male Wistar rats were randomly allocated into four groups (n = 8): sham-operated, varicocele (VC), varicocele treated with minocycline (VC + MINO, 40 mg/kg/i.p.), and minocycline-only (MINO). After 8 weeks, assessments included serum levels of testosterone, Luteinizing Hormone (LH), and Follicle-stimulating hormone (FSH); sperm analysis (count, motility, morphology); testicular histopathology; and mRNA/protein expression of luteinizing hormone/choriogonadotropin receptor (LHCGR), Follicle Stimulating Hormone Receptor (FSHR), Steroidogenic factor-1 (SF-1), CatSper-1, and CatSper-2. Results: Induction of varicocele significantly reduced serum testosterone levels but increased LH and FSH levels, impaired all sperm quality parameters, and caused severe testicular damage with decreased germ and Sertoli cell counts. These effects were paralleled by significant downregulation of LHCGR, FSHR, SF-1, CatSper-1, and CatSper-2 expression. Minocycline treatment in the VC + MINO group effectively counteracted these alterations, leading to a significant increase in testosterone, a reduction in LH and FSH, improved sperm quality, reduced histological damage, and upregulation of the studied receptors and channels compared with the untreated VC group. Conclusions: Minocycline demonstrates a protective role against varicocele-induced testicular injury by improving sperm quality, restoring hormonal balance, and upregulating the expression of genes critical for steroidogenesis and sperm function. These findings highlight its potential as a novel therapeutic agent for managing varicocele-associated male infertility.

Resumen

Antecedentes: El varicocele, una causa común de infertilidad masculina, deteriora la función reproductiva a través del estrés oxidativo y la alteración del eje hipotálamo-hipófisis-gonadal (HPG). La minociclina, un antibiótico tetraciclínico, posee potentes propiedades antioxidantes y anti-apoptóticas más allá de sus efectos antimicrobianos. Este estudio tuvo como objetivo evaluar los posibles efectos protectores de la minociclina sobre los parámetros espermáticos, los niveles hormonales y la expresión de receptores hormonales clave y canales iónicos en un modelo de rata con varicocele. Métodos: Treinta y dos ratas Wistar macho fueron asignadas aleatoriamente a cuatro grupos (n = 8): operadas simuladamente (sham), con varicocele (VC), con varicocele tratadas con minociclina (VC + MINO, 40 mg/kg/i.p.) y solo con minociclina (MINO). Tras 8 semanas, las evaluaciones incluyeron los niveles séricos de testosterona, Luteinizing Hormone (LH) y Follicle-stimulating hormone (FSH); análisis espermático (recuento, motilidad, morfología); histopatología testicular; y expresión de ARNm/proteína de luteinizing hormone/choriogonadotropin receptor (LHCGR), Follicle Stimulating Hormone Receptor (FSHR), Steroidogenic factor-1 (SF-1), CatSper-1 y CatSper-2. Resultados: La inducción de varicocele redujo significativamente los niveles séricos de testosterona, pero aumentó los de LH y FSH, deterioró todos los parámetros de calidad espermática y causó daño testicular severo con disminución del recuento de células germinales y de Sertoli. Estos efectos se acompañaron de una regulación negativa significativa de la expresión de LHCGR, FSHR, SF-1, CatSper-1 y CatSper-2. El tratamiento con minociclina en el grupo VC + MINO contrarrestó eficazmente estas alteraciones, conduciendo a un aumento significativo de la testosterona, una reducción de la LH y la FSH, una mejoría de la calidad espermática, una reducción del daño histológico y una regulación positiva de los receptores y canales estudiados, en comparación con el grupo VC no tratado. Conclusiones: La minociclina demuestra un papel protector contra la lesión testicular inducida por varicocele, mejorando la calidad espermática, restaurando el equilibrio hormonal y regulando positivamente la expresión de genes críticos para la esteroidogénesis y la función espermática. Estos hallazgos resaltan su potencial como un nuevo agente terapéutico para el manejo de la infertilidad masculina asociada al varicocele.

Minocycline; Male infertility; Hormonal receptor; Varicocele

Palabras Clave

Minociclina; Infertilidad masculina; Receptor hormonal; Varicocele

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