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Updated: Jun 6, 2026

Measuring Sperm Guidance and Motility within the Caenorhabditis elegans Hermaphrodite Reproductive Tract
Published on: June 6, 2019
Aquaporin3 is a sperm water channel essential for postcopulatory sperm osmoadaptation and migration
Qi Chen1, Hongying Peng, Li Lei
1State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Abstract:
In the journey from the male to female reproductive tract, mammalian sperm experience a natural osmotic decrease (e.g., in mouse, from ~415 mOsm in the cauda epididymis to ~310 mOsm in the uterine cavity). Sperm have evolved to utilize this hypotonic exposure for motility activation, meanwhile efficiently silence the negative impact of hypotonic cell swelling. Previous physiological and pharmacological studies have shown that ion channel-controlled water influx/efflux is actively involved in the process of sperm volume regulation; however, no specific sperm proteins have been found responsible for this rapid osmoadaptation. Here, we report that aquaporin3 (AQP3) is a sperm water channel in mice and humans. Aqp3-deficient sperm show normal motility activation in response to hypotonicity but display increased vulnerability to hypotonic cell swelling, characterized by increased tail bending after entering uterus. The sperm defect is a result of impaired sperm volume regulation and progressive cell swelling in response to physiological hypotonic stress during male-female reproductive tract transition. Time-lapse imaging revealed that the cell volume expansion begins at cytoplasmic droplet, forcing the tail to angulate and form a hairpin-like structure due to mechanical membrane stretch. The tail deformation hampered sperm migration into oviduct, resulting in impaired fertilization and reduced male fertility. These data suggest AQP3 as an essential membrane pathway for sperm regulatory volume decrease (RVD) that balances the "trade-off" between sperm motility and cell swelling upon physiological hypotonicity, thereby optimizing postcopulatory sperm behavior.
Insights
Aquaporin3 (AQP3) is identified as a crucial sperm water channel. AQP3 deficiency impairs sperm volume regulation, leading to tail deformation, reduced fertilization, and infertility in mice.
Area of Science:
- Reproductive Biology
- Cell Physiology
- Membrane Transport
Background:
- Mammalian sperm undergo osmotic changes in the female reproductive tract, requiring efficient volume regulation for motility and function.
- While ion channels are known to be involved in sperm volume control, specific proteins responsible for osmoadaptation remain unidentified.
Purpose of the Study:
- To identify the specific sperm water channel responsible for osmoadaptation in mammalian sperm.
- To investigate the role of aquaporin3 (AQP3) in sperm volume regulation and its impact on male fertility.
Main Methods:
- Utilized Aqp3-deficient mice to study sperm behavior and volume regulation under hypotonic conditions.
- Employed time-lapse imaging to observe sperm morphology and tail dynamics during hypotonic stress.
- Assessed sperm motility, fertilization capacity, and overall male fertility in Aqp3-deficient models.
Main Results:
- Aquaporin3 (AQP3) was confirmed as a functional water channel in mouse and human sperm.
- Aqp3-deficient sperm exhibited impaired regulatory volume decrease (RVD) and excessive swelling in hypotonic environments.
- Sperm tail deformation, characterized by hairpin-like angulation, was observed in Aqp3-deficient sperm due to mechanical membrane stretch.
- This tail deformation significantly hampered sperm migration and reduced fertilization rates, leading to decreased male fertility.
Conclusions:
- AQP3 is essential for maintaining sperm volume homeostasis during the transition to the female reproductive tract.
- The identified AQP3 pathway balances sperm motility activation with the prevention of detrimental cell swelling.
- Dysfunctional AQP3 compromises postcopulatory sperm behavior and male reproductive success.
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