TFEB Deficiency Impairs Male Fertility Through Mitochondrial Dysfunction
Hongxia Li1,2, Guoqing Zhao3, Ruojun Zong4
1Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, China.
Summary
Transcription Factor EB (TFEB) loss impairs male fertility by disrupting testicular mitochondria. This leads to reduced sperm quality and hormone production, highlighting TFEB's crucial role in male reproductive health.
Area of Science:
- Reproductive Biology
- Molecular Endocrinology
- Mitochondrial Biology
Background:
- Transcription Factor EB (TFEB) regulates lysosomal and autophagic pathways.
- TFEB is highly expressed in testes, but its role in male fertility is unknown.
Purpose of the Study:
- To investigate the function of TFEB in spermatogonia and its impact on male fertility.
- To elucidate the molecular mechanisms underlying TFEB-mediated male reproductive regulation.
Main Methods:
- Spermatogonia-specific TFEB deletion in mice.
- Assessment of fertility, sperm parameters, and androgen production.
- Immunofluorescence, electron microscopy, transcriptomic, and biochemical analyses.
Main Results:
- TFEB deletion caused impaired fertility, reduced sperm motility, and lower androgen levels.
- Decreased expression of spermiogenesis marker TNP1 was observed.
- Mitochondrial abnormalities and dysregulation of steroidogenic and calcium homeostasis pathways were identified.
Conclusions:
- TFEB is essential for maintaining testicular mitochondrial integrity and function.
- Loss of TFEB leads to male subfertility via metabolic and hormonal dysregulation.
- TFEB is a critical regulator of male reproductive health.
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