In the United States, around 9% of men and 11% of women of reproductive age struggle with fertility issues. This often happens because sperm and eggs fail to recognize, stick, or fuse correctly. A key part of this process involves two proteins: IZUMO1 on sperm cells and JUNO on eggs. These proteins help sperm and eggs recognize and fuse with each other.
One known disruptor of this connection is a sperm antibody called OBF13, which was discovered 40 years ago at Osaka University in Japan. While it was known that OBF13 could interfere with fertilization, the exact details were unclear.
A dedicated team of researchers at Yale University has made a remarkable discovery that could change the lives of many struggling with fertility issues. They’ve identified a natural biological mechanism that prevents sperm cells from interacting with eggs, effectively stopping fertilization.
This discovery was made in rodent models. It holds immense promise for developing new treatments for those facing fertility challenges and creating innovative contraceptive therapies.
Females supercharge sperm evolution, especially in animals
“This will have direct implications for infertility and contraception research, especially immuno-infertility and immuno-contraception,” said Steven Tang, an assistant professor of molecular biophysics and biochemistry at Yale and the study’s corresponding author.
The researchers studied the X-ray structure of IZUMO1 when it interacts with OBF13. They discovered that OBF13 attaches to sperm and changes how sperm and egg come into contact. They also identified a strong version of OBF13 that can block fertilization.
Furthermore, they found important sites on the JUNO protein that allow it to bind with IZUMO1. These sites enable sperm and egg to bind for fertilization, even when OBF13 or its variant is present.
“In this work, we are reporting the first anti-sperm antibody-antigen complex structure. We provide high-resolution information that will open avenues for discovering IZUMO1 regulators, guide antibody and small-molecule inhibitor design, and support drug screening for contraceptive development,” Tang explained.
Journal Reference
- Kaneda, Y., Lu, Y., Sun, J., Shimada, K., Emori, C., Noda, T., Koyano, T., Matsuyama, M., Miyata, H., & Ikawa, M. (2025). TEX38 localizes ZDHHC19 to the plasma membrane and regulates sperm head morphogenesis in mice. Proceedings of the National Academy of Sciences, 122(10), e2417943122. DOI: 10.1073/pnas.2417943122
