A breakthrough study from Osaka University has uncovered a critical protein interaction essential for sperm development, shedding new light on the complex mechanisms behind male fertility. The research, soon to be published in Proceedings of the National Academy of Sciences (PNAS), identifies a crucial interaction between two proteins, TEX38 and ZDHHC19, that regulate sperm cell maturation.
Sperm development, or spermatogenesis, involves intricate cellular changes, including the reshaping of the sperm head, the creation of the sperm tail, and the shrinking of the nucleus. Disruptions in any of these processes can lead to malformed, nonfunctional sperm and ultimately male infertility.
Lead author Yuki Kaneda explained, “While several genes critical to spermiogenesis have been identified, much is still unknown about the molecular pathways that guide sperm development.”
In their study, the team focused on the protein TEX38, which is primarily expressed in the testes. When TEX38 was removed in mice, the resulting sperm exhibited abnormal head shapes, leading to infertility. The researchers then turned their attention to the proteins interacting with TEX38 to better understand the underlying cause.
“We were amazed by the results,” said Masahito Ikawa, senior author of the study. “TEX38 interacts with ZDHHC19, and deleting either of these proteins produced the same sperm deformity. Additionally, if one of these proteins was absent, the other was present in significantly lower amounts.”
ZDHHC19 plays a key role in adding lipids to proteins through a process called S-palmitoylation. It specifically modifies ARRDC5, a protein known to be vital for sperm development. When ZDHHC19 was inhibited, the same deformities in sperm occurred, as the necessary cytoplasm removal from the sperm head did not occur.
“Our findings reveal that TEX38 and ZDHHC19 form an essential complex in sperm development,” said Kaneda. “This complex regulates the S-palmitoylation of proteins critical to ensuring sperm maintain the correct shape and functionality.”
This discovery provides significant insight into the molecular causes of male infertility. Understanding these processes could pave the way for the development of male contraceptives that work by inhibiting lipid modifications, thus impairing sperm development and reducing fertility.
Related topics:
Florence Pugh Opens Up About Freezing Her Eggs After Diagnosed with PCOS and Endometriosis
Amol Rajan Shares IVF Struggles and Grief Over Father’s Death
