Understanding the Role of Protein Palmitoylation in Sperm Motility

This research is the first to detail the in situ locations and dynamic changes of protein palmitoylation in sperm, elucidating its crucial role in sperm motility and potential mechanisms involved. The findings suggest possible applications for addressing male infertility.
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BioMed Central
BioMed Central BioMed Central

Protein palmitoylation is involved in regulating mouse sperm motility via the signals of calcium, protein tyrosine phosphorylation and reactive oxygen species - Biological Research

Background Protein palmitoylation, a critical posttranslational modification, plays an indispensable role in various cellular processes, including the regulation of protein stability, mediation of membrane fusion, facilitation of intracellular protein trafficking, and participation in cellular signaling pathways. It is also implicated in the pathogenesis of diseases, such as cancer, neurological disorders, inflammation, metabolic disorders, infections, and neurodegenerative diseases. However, its regulatory effects on sperm physiology, particularly motility, remain unclear. This study aimed to elucidate the mechanism by which protein palmitoylation governs sperm motility. Methods Protein palmitoylation in situ in mouse sperm was observed using innovative click chemistry. Sperm motility and motion parameters were evaluated using a computer-assisted sperm analyzer (CASA) after treatment with 2-bromopalmitic acid (2BP), a specific inhibitor of protein palmitoylation. Protein palmitoylation levels were confirmed by the acyl-biotin exchange (ABE) method. The interplay between protein palmitoylation, protein tyrosine phosphorylation, and intracellular calcium was investigated using Western blotting, ABE method, and fluorescent probes. The regulation of reactive oxygen species was also examined using fluorescent probes. Results Localized patterns and dynamics of protein palmitoylation in distinct sperm regions were revealed, including the midpiece, post-acrosomal region, acrosome, and head. Alterations in protein palmitoylation in sperm were observed under in vitro physiological conditions. Treatment with 2BP significantly affected sperm motility and motion parameters. The study revealed interactions between protein palmitoylation, including heat shock protein 90, and protein kinase A/protein kinase C-associated protein tyrosine phosphorylation and intracellular calcium. Additionally, protein palmitoylation was found to be involved in reactive oxygen species regulation. Conclusions Protein palmitoylation regulates sperm motility through calcium signaling, protein tyrosine phosphorylation, and reactive oxygen species. This study revealed the characteristics of protein palmitoylation in sperm and its role in regulating sperm motility, thereby providing novel insights into the causes of asthenozoospermia associated with sperm motility in humans.

What is Protein Palmitoylation?

Protein palmitoylation is a process where a fatty acid, palmitic acid, is attached to proteins, affecting their function and location within cells. This modification is essential for various biological processes, including protein stability and cellular signaling.

Why is Sperm Motility Important?

Sperm motility is essential for male fertility. For sperm to successfully reach and fertilize an egg, they must be able to swim effectively through the female reproductive tract. Only those sperm that exhibit optimal motility can navigate through the cumulus cell layer and zona pellucida to achieve fertilization. Therefore, understanding the factors that influence sperm motility is critical for addressing issues related to male infertility.

Impact of Protein Palmitoylation on Sperm Motility

The study reveals that protein palmitoylation significantly influences sperm motility. Researchers observed that altering palmitoylation levels in mouse sperm affected their movement and overall motility parameters. This finding is crucial, as sperm motility is a key determinant of male fertility. 

Mechanisms Involved

Calcium Signaling: Calcium ions play a vital role in sperm function. The study found that protein palmitoylation interacts with calcium signaling pathways, which are essential for sperm viability and motility.
Protein Tyrosine Phosphorylation: This process is linked to the activation of signaling pathways that enhance sperm function. The research indicates that protein palmitoylation is involved in regulating these phosphorylation events.
Reactive Oxygen Species (ROS): While ROS can enhance sperm viability at low levels, excessive ROS can be detrimental. The study suggests that protein palmitoylation also plays a role in managing ROS levels within sperm.
figure 10

Schematic representation of the involvement of protein palmitoylation in sperm motility

Xiong, one of the lead authors, stated, “Our findings reveal the complex interplay between protein modifications and sperm function, emphasizing the importance of palmitoylation in male reproduction." And co-author Yi added, “Understanding these mechanisms opens new avenues for addressing male infertility, which is often overlooked in reproductive health discussions.”

Future Directions

The research team encourages further exploration into the role of protein palmitoylation in other aspects of reproductive biology and its potential implications in treating male infertility. They also highlight the need for interdisciplinary collaboration to deepen our understanding of sperm physiology. The intricate relationship between protein modifications and sperm function is a promising area for future research and discussion. By continuing to explore these connections, we can better understand the complexities of male reproduction and work towards improving reproductive health outcomes.

The full article is available for free under a Creative Commons license, allowing for broader access to the findings. You can read it here.

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Biomedical Research
Life Sciences > Health Sciences > Biomedical Research
Reproductive Physiology
Life Sciences > Biological Sciences > Physiology > Reproductive Physiology
Male Factor Infertility
Life Sciences > Health Sciences > Clinical Medicine > Diseases > Urogenital Diseases > Male Factor Infertility
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