Proca1, also known as protein interacting with cyclin A1, has diverse functions. It has been implicated in various biological processes including fatty acid metabolism-related pathways, which may impact anti-PD1 therapy efficacy in oral tongue squamous cell carcinoma [1]. It is also potentially involved in male infertility, with its expression in the testis, specifically localized to the acrosome of normal human sperm [2,3].

In male infertility research, three patients with acrosome-deficient teratozoospermia were found to have PROCA1 mutations by whole exome sequencing. However, Proca1 knockout (KO) mice generated using CRISPR-Cas9 technology were fertile, with no significant differences in testicular tissue, sperm morphology, or acrosome marker expression compared to wild-type mice. This suggests that the PROCA1 mutation identified in humans may not affect acrosome biogenesis in mice [3].

In conclusion, Proca1 plays potential roles in fatty acid metabolism-related immunotherapy responses and male infertility. The Proca1 KO mouse model has been valuable in revealing that the human PROCA1 mutation may not impact acrosome formation in mice, contributing to our understanding of its function in male infertility.

References:

1. Tan, Xiyan, Li, Guoli, Deng, Honghao, Zhang, Chenzhi, Chen, Yanfeng. . Obesity enhances the response to neoadjuvant anti-PD1 therapy in oral tongue squamous cell carcinoma. In Cancer medicine, 13, e7346. doi:10.1002/cam4.7346. https://pubmed.ncbi.nlm.nih.gov/38923758/

2. Omolaoye, Temidayo S, Omolaoye, Victor A, Kandasamy, Richard K, Hachim, Mahmood Yaseen, Du Plessis, Stefan S. 2022. Omics and Male Infertility: Highlighting the Application of Transcriptomic Data. In Life (Basel, Switzerland), 12, . doi:10.3390/life12020280. https://pubmed.ncbi.nlm.nih.gov/35207567/

3. Zheng, Na, Shen, Yiru, Wang, Yu, Zhu, Fuxi, Cao, Yunxia. 2024. Unraveling the Impact of the PROCA1 Mutation in Male Infertility: Incorporating Whole Exome Sequencing in Teratozoospermia Patients and Analyzing Proca1 Knockout Mice. In Reproductive sciences (Thousand Oaks, Calif.), 32, 1080-1091. doi:10.1007/s43032-024-01624-6. https://pubmed.ncbi.nlm.nih.gov/38867036/