Mysterious sperm structure offers new insights on infertility

Researchers at Michigan State University (MSU) have made a significant breakthrough in understanding a mysterious sperm structure known as the cytoplasmic droplet (CD), potentially offering new insights into infertility.

The cytoplasmic droplet, a poorly understood feature found in mammalian sperm, including humans, is located near the sperm’s head. Despite being discovered over a century ago, its formation and function remained unclear due to limited molecular and genetic tools for its study. 

Focus of the research

The new research was led by Professor Chen Chen from the Department of Animal Science and the Reproductive and Developmental Sciences Program at MSU’s College of Agriculture and Natural Resources. 

Professor Chen said that while scientists have often disregarded the cytoplasmic droplet, it can no longer be ignored.

“Our new study using mice shows that the cytoplasmic droplet is indeed an actively forming organelle purposefully designed to regulate sperm maturation and fertility,” said Chen. 

“It acts as a ‘storage room’ to pack up critical proteins needed for sperm function before its long journey to reach the egg. It’s like packing for a trip to Mars – the spaceship needs to load up everything needed for the journey before leaving Earth.”  

Unique trafficking system

A novel aspect of Chen’s research is the discovery of a unique protein trafficking system within developing sperm. This system, controlled by the SYPL1 gene, actively transports essential proteins via small membrane vesicles to the cytoplasmic droplet. 

Chen compares these vesicles to cargo trucks delivering protein cargos to the sperm storage room. The SYPL1 protein, residing on these vesicles, is crucial in directing them to the cytoplasmic droplet.

Critical insights 

Chen noted that when the SYPL1 gene is deleted in mice, this protein trafficking system collapses, and critical metabolic enzymes and essential proteins fail to be shipped to the cytoplasmic droplet, resulting in an empty cytoplasmic droplet devoid of vesicles – something he had never seen before. 

This results in mutant sperm losing motility and the ability to adapt to osmotic changes, ultimately causing infertility.

Study implications 

“I believe this study represents a breakthrough in understanding the cytoplasmic droplet formation and its potential function,” Chen said. “At the cellular level, it helps us realize that there is a specialized protein trafficking system that actively transports cargos to the cytoplasmic droplet for future use by sperm for their journey to the egg. 

“Fundamentally, this finding will change people’s misconception about this mysterious sperm structure. It will open new avenues for research on the cytoplasmic droplet as a biomarker for fertility in humans and animals and, possibly, on targeting this novel pathway for fertility control.” 

The research offers a promising new perspective on a long-overlooked aspect of reproductive biology, with potential implications for understanding and treating infertility.

The study is published in the journal Nature Communications.

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