Background: During sperm capacitation, post-translational modifications such as SUMOylation are crucial for maintaining protein homeostasis. Macroautophagy (autophagy) is essential for cellular and energy homeostasis, aiding in the survival of reproductive cells and protecting against ovarian aging. However, the role of autophagy in capacitated sperm remains unclear.
Objectives: This study aimed to explore the relationship between small ubiquitin-like modifier 1 (SUMO1)-modified proteins and autophagy during sperm capacitation, focusing on the involvement of immunoglobulin-binding protein 1 (IGBP1) in the autophagy pathway.
Materials and methods: Tandem mass spectrometry was employed to identify SUMO1-modified proteins in boar sperm before and after capacitation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted to investigate the involvement of these proteins in autophagy, specifically examining the modification and degradation of IGBP1 via the ubiquitin-proteasome pathway (UPP). The regulatory role of the PKA-mTOR signaling axis on autophagy during capacitation was also examined.
Results: A total of 229 SUMO1-modified proteins were identified in the non-capacitated group and 197 in the capacitated group, with 77 proteins unique to the non-capacitated state and 45 unique to the capacitated state. IGBP1 was found to be involved in the autophagy pathway, and its SUMO1 modification level significantly decreased after sperm capacitation, leading to its degradation via UPP. This degradation promoted autophagy and increased mTOR activity. The autophagy process involving IGBP1 was regulated by the upstream PKA-mTOR signaling axis. Additionally, a negative correlation between autophagy and apoptosis was observed during sperm capacitation, where the activation of autophagy enhanced capacitation and improved sperm-egg binding and embryonic development.
Conclusion: The degradation of de-SUMOylated IGBP1 via UPP promotes sperm autophagy and enhances in vitro capacitation, providing new insights into the molecular mechanisms of sperm capacitation.
Keywords: IGBP1; UPP; autophagy; boar sperm capacitation; mTOR.
© 2025 American Society of Andrology and European Academy of Andrology.