Autophagy Mechanisms in Male Reproductive Biology

Autophagy is a conserved cellular recycling process that modulates protein and organelle turnover to maintain homeostasis under basal and stress conditions. In the male reproductive system, autophagy plays pivotal roles at multiple stages, from the hypothalamic-pituitary-testis axis to sperm maturation and fertilisation. Within the testis, autophagy regulates spermatogonial stem cell proliferation, meiotic progression and chromatoid body remodelling in round spermatids. During spermiogenesis, key autophagy factors contribute to acrosome biogenesis, flagellar assembly, head shaping and cytoplasm removal from elongating spermatids. In post-testicular phases, autophagic machinery influences capacitation, acrosome reaction and the clearance of paternal mitochondria after fertilisation. Beyond germ cells, autophagy in Sertoli and Leydig cells supports phagocytic clearance of apoptotic remnants, steroid hormone production and mitochondrial quality control. Dysregulation of these processes is implicated in declining sperm counts, impaired motility and idiopathic infertility, highlighting autophagy as both a biomarker and a therapeutic target in male reproductive health.

Research from Nature Portfolio

Recent studies have demonstrated that specialised autophagy pathways are integral to Sertoli cell function and sperm physiology. Work in a mouse model revealed that microRNA-mediated downregulation of autophagy proteins impairs LC3-associated phagocytosis in Sertoli cells, leading to defective clearance of apoptotic germ cells and compromised fertility. In human spermatozoa, functional assays showed that autophagy-related proteins, including LC3, Beclin-1 and p62, are present and modulate motility and viability through a mitophagy-like process that influences mitochondrial protein turnover. Foundational experiments in rat Sertoli cells further established that testosterone controls the autophagic clearance of androgen-binding protein, thereby regulating intratesticular hormone availability and Sertoli cell support of spermatogenesis.

Autophagy Mechanisms in Male Reproductive Biology publication trend

The graph below shows the total number of articles in autophagy mechanisms in male reproductive biology across all publications each year (not limited to Nature Index journals).

Technical terms

Autophagy: A lysosome-dependent degradation pathway that recycles intracellular components to maintain cellular homeostasis.

Autophagosome: A double-membrane vesicle that sequesters cytoplasmic cargo for delivery to the lysosome.

LC3: Microtubule-associated protein 1 light chain 3, a ubiquitin-like protein that undergoes lipidation to mark autophagosome membranes.

Acrosome: A specialised secretory organelle in the sperm head containing enzymes required for zona pellucida penetration.

Mitophagy: Selective autophagic removal of damaged or supernumerary mitochondria to preserve mitochondrial function and quality.

References

1. Treatment with Pterostilbene Ameliorates the Antioxidant Status of Bovine Spermatozoa and Modulates Cell Death Pathways. Antioxidants (2024).
2. Ubiquitin Ligase Nrdp1 Controls Autophagy-Associated Acrosome Biogenesis and Mitochondrial Arrangement during Spermiogenesis. Cells (2023).
3. The Autophagy Marker LC3 Is Processed during the Sperm Capacitation and the Acrosome Reaction and Translocates to the Acrosome Where It Colocalizes with the Acrosomal Membranes in Horse Spermatozoa. International Journal of Molecular Sciences (2023).
4. Autophagy-related proteins are functionally active in human spermatozoa and may be involved in the regulation of cell survival and motility. Scientific Reports (2016).
5. Testosterone regulates the autophagic clearance of androgen binding protein in rat Sertoli cells. Scientific Reports (2015).
6. Cross-talk between miR-471-5p and autophagy component proteins regulates LC3-associated phagocytosis (LAP) of apoptotic germ cells. Nature Communications (2017).