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Espermatozoides astenozoospérmicos manifiestan disfunción mitocondrial y la deficiencia de DKK3 es un factor
Ruizhi Xue1, Longlong Zhang1, Ruikang Shi2
1Department of Urology and Andrology, Xijing Hospital of the Air Force Medical University, Xi'an, 710032, China.
Reproduction (Cambridge, England)
|January 30, 2026
Resumen
La astenozoospermia (AS), una causa de infertilidad masculina, implica una producción de energía deficiente en los espermatozoides y un aumento del estrés oxidativo. La deficiencia de Dickkopf (DKK)3 contribuye a la AS al alterar la función mitocondrial y la motilidad de los espermatozoides.
Área de la Ciencia:
- Biología Reproductiva; Metabolismo Mitocondrial; Infertilidad Masculina
Sus antecedentes:
- La astenozoospermia (AS) es una causa importante de infertilidad masculina, pero sus bases metabólicas no se comprenden completamente.; La comprensión de los perfiles metabólicos de los espermatozoides es crucial para el diagnóstico y tratamiento de la AS.
Objetivo del estudio:
- Definir el perfil metabólico energético de los espermatozoides con AS.; Identificar las proteínas clave relacionadas con las desregulaciones metabólicas en la AS.; Investigar el papel de Dickkopf (DKK)3 en la patogénesis de la AS.
Principales métodos:
- Análisis comparativo del metabolismo energético de los espermatozoides (producción de ATP, actividad de la ETC, ROS, MMP) entre pacientes con AS y controles.; Análisis proteómico para identificar proteínas expresadas diferencialmente (DEPs) en espermatozoides con AS.; Análisis de enriquecimiento funcional y de correlación para vincular las DEPs con los parámetros metabólicos.; Caracterización fenotípica de ratones knockout de Dkk3.
Principales resultados:
- Los espermatozoides con AS presentan una reducción del ATP derivado de la fosforilación oxidativa (OXPHOS), una actividad disminuida de la cadena de transporte de electrones (ETC), una disminución del potencial de membrana mitocondrial (MMP) y un aumento de las especies reactivas de oxígeno (ROS).; El análisis proteómico identificó 205 DEPs, con la vía de la respiración aeróbica significativamente enriquecida.; Seis DEPs, incluido Dickkopf (DKK)3, se correlacionaron significativamente con el ATP de OXPHOS y el MMP.; Los ratones knockout de Dkk3 mostraron una motilidad reducida de los espermatozoides y disfunción mitocondrial, lo que refleja los fenotipos de AS.
Conclusiones:
- El deterioro de la bioenergética mitocondrial y el aumento de las ROS son características clave de la AS.; La deficiencia de DKK3 está implicada en la patogénesis de la AS, potencialmente a través de la disfunción mitocondrial.; DKK3 desempeña un papel fundamental en el mantenimiento de la función mitocondrial y la motilidad de los espermatozoides.
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