News | Osaka University Study Identifies Key Protein Complex in Sperm Morphology, Offering New Insights into Male Infertility and Contraception
Every developmental step in the human reproductive system is tightly regulated by molecular mechanisms. A multi-institutional team led by Osaka University in Japan has revealed for the first time how the interaction between two key proteins shapes sperm morphology. The forthcoming PNAS study found that dysfunction of this protein complex deforms the sperm head and causes male infertility.
"We know that sperm formation is extremely complex and involves nuclear condensation, tail formation, and head remodeling," said first author Yuki Kaneda of Osaka University. "But many of the molecular mechanisms that determine this process remain unknown."
To identify factors behind abnormal sperm morphology, the team first knocked out TEX38, a protein expressed mainly in the testes, in mice. The sperm produced by these mice had heads severely bent backward and could not fertilize normally, resulting in infertility.
To understand why TEX38 is critical to sperm morphology, the researchers screened its interacting proteins. They found that TEX38 works closely with another protein enzyme, ZDHHC19. Mice lacking either protein produced sperm with the same bent-head abnormality. When one protein was absent, expression of the other also declined significantly.
Masahito Ikawa, senior professor and reproductive biologist at Osaka University's Research Institute for Microbial Diseases, said: "We found that TEX38 and ZDHHC19 are highly interdependent. They are present together in developing sperm and must work in coordination to produce normally structured sperm."
ZDHHC19 is an enzyme involved in S-palmitoylation, which adds lipids to proteins to regulate their function. The researchers confirmed that ZDHHC19 performs lipid modification of ARRDC5, a protein essential for sperm development. When this process is disrupted, the sperm head develops the same abnormality seen with TEX38 deficiency: it cannot remove excess cytoplasm, and development fails.
"Our results show that TEX38 and ZDHHC19 form a stable complex that regulates lipid modification of key proteins during the formation of sperm morphology," Kaneda concluded.
Because sperm structure and morphology directly affect motility and fertilization potential, the study offers new insight into the molecular causes of male infertility and possible future male contraceptive strategies. For example, targeting the complex's lipid-modification function might enable reversible contraception without altering hormone levels.
News | Osaka University Study Identifies Key Protein Complex in Sperm Morphology, Offering New Insights into Male Infertility and Contraception
News | Osaka University Study Identifies Key Protein Complex in Sperm Morphology, Offering New Insights into Male Infertility and Contraception
Every developmental step in the human reproductive system is tightly regulated by molecular mechanisms. A multi-institutional team led by Osaka University in Japan has revealed for the first time how the interaction between two key proteins shapes sperm morphology. The forthcoming PNAS study found that dysfunction of this protein complex deforms the sperm head and causes male infertility.
"We know that sperm formation is extremely complex and involves nuclear condensation, tail formation, and head remodeling," said first author Yuki Kaneda of Osaka University. "But many of the molecular mechanisms that determine this process remain unknown."
To identify factors behind abnormal sperm morphology, the team first knocked out TEX38, a protein expressed mainly in the testes, in mice. The sperm produced by these mice had heads severely bent backward and could not fertilize normally, resulting in infertility.
To understand why TEX38 is critical to sperm morphology, the researchers screened its interacting proteins. They found that TEX38 works closely with another protein enzyme, ZDHHC19. Mice lacking either protein produced sperm with the same bent-head abnormality. When one protein was absent, expression of the other also declined significantly.
Masahito Ikawa, senior professor and reproductive biologist at Osaka University's Research Institute for Microbial Diseases, said: "We found that TEX38 and ZDHHC19 are highly interdependent. They are present together in developing sperm and must work in coordination to produce normally structured sperm."
ZDHHC19 is an enzyme involved in S-palmitoylation, which adds lipids to proteins to regulate their function. The researchers confirmed that ZDHHC19 performs lipid modification of ARRDC5, a protein essential for sperm development. When this process is disrupted, the sperm head develops the same abnormality seen with TEX38 deficiency: it cannot remove excess cytoplasm, and development fails.
"Our results show that TEX38 and ZDHHC19 form a stable complex that regulates lipid modification of key proteins during the formation of sperm morphology," Kaneda concluded.
Because sperm structure and morphology directly affect motility and fertilization potential, the study offers new insight into the molecular causes of male infertility and possible future male contraceptive strategies. For example, targeting the complex's lipid-modification function might enable reversible contraception without altering hormone levels.
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