LYPD4, or LY6/PLAUR domain containing 4, is a gene encoding a protein expressed specifically in the testes and sperm in humans and conserved in mammals. It is essential for male fertility, playing a crucial role in sperm fertilizing ability. It is involved in processes related to sperm migration in the female reproductive tract and sperm-zona interaction [1].

Gene knockout (KO) mouse models have been pivotal in understanding LYPD4's function. Lypd4 KO mice are infertile despite normal sperm number and motility. The mutant sperm fails to reach the oviduct during migration in the female reproductive tract, leading to fertilization failure. Also, these sperms cannot fertilize denuded eggs via in vitro fertilization (IVF) but can fertilize eggs within an intact Cumulus-Oocyte Complex, suggesting its role in sperm-zona interaction. Mass spectrometry analysis of KO sperm showed changes in a small subset of proteins (26 proteins), including significant reduction of ADAM3, a key fertilization complex component [1].

In conclusion, LYPD4 is essential for mammalian fertilization, particularly in sperm migration and sperm-zona binding. Insights from Lypd4 KO mouse models contribute to understanding the molecular mechanisms of male infertility, which may offer potential strategies to improve IVF success rates [1]. Additionally, associations between LYPD4 and other conditions such as inflammation in critical illness and resilience in the German population have been reported, although the exact mechanisms are yet to be fully elucidated [2,3].

References:

1. Wang, Dan, Cheng, Liping, Xia, Wenjuan, Guo, Xuejiang, Xu, Eugene Yujun. . LYPD4, mouse homolog of a human acrosome protein, is essential for sperm fertilizing ability and male fertility†. In Biology of reproduction, 102, 1033-1044. doi:10.1093/biolre/ioaa018. https://pubmed.ncbi.nlm.nih.gov/32040177/

2. El-Dehaibi, Fayten, Zamora, Ruben, Radder, Josiah, Kitsios, Georgios D, Vodovotz, Yoram. 2023. A common single nucleotide polymorphism is associated with inflammation and critical illness outcomes. In iScience, 26, 108333. doi:10.1016/j.isci.2023.108333. https://pubmed.ncbi.nlm.nih.gov/38034362/

3. Herrera-Rivero, Marisol, Garvert, Linda, Horn, Katrin, Baune, Bernhard T, Berger, Klaus. 2024. A meta-analysis of genome-wide studies of resilience in the German population. In Molecular psychiatry, 30, 497-505. doi:10.1038/s41380-024-02688-1. https://pubmed.ncbi.nlm.nih.gov/39112778/

4. Fujihara, Yoshitaka, Noda, Taichi, Kobayashi, Kiyonori, Matzuk, Martin M, Ikawa, Masahito. 2019. Identification of multiple male reproductive tract-specific proteins that regulate sperm migration through the oviduct in mice. In Proceedings of the National Academy of Sciences of the United States of America, 116, 18498-18506. doi:10.1073/pnas.1908736116. https://pubmed.ncbi.nlm.nih.gov/31455729/