Combining Bioinformatics and Antibody-Based Approaches to Characterize Novel Sperm Proteins Involved in Human Fertility

VERÓN, GUSTAVO LUIS; VAZQUEZ-LEVIN, MÓNICA HEBE

Seminario; Presentation at the Swiss Institute of Bioinformatics; 2018

Swiss Institute of Bioinformatics

Infertility affects up to one in six couples, with alterations in the male partner contributing up to half of the cases, and this is expected to worsen as a result of diseases, lifestyle and delayed parenthood. However, the molecular entities that give sperm their fertilizing potential are poorly characterized or still unknown. In particular, several entities related to sperm motility, a fundamental sperm function to reach and penetrate the oocyte, as well as those involved in sperm capacitation and acrosome reaction, both mandatory changes for sperm recognition and interaction with the oocyte vestments, are still unknown. In recent years, approaches involving bioinformatics, transcriptomics and proteomics have been used to describe the protein repertoire of the testicular germ cell lineage. Many of the identified proteins are still poorly characterized, and some of them that are secreted or located in the plasma membrane may be involved in fertility-linked events. In this project, we propose to perform deep data mining analyses on about 200 such proteins identified as highly expressed in male reproductive tissues, in order to select 10-15 candidates that will be functionally tested on human sperm cells using antibody-based assays. It is a new collaborative initiative between the Swiss Institute of Bioinformatics (SIB) and Instituto de Biología y Medicina Experimental (IBYME) from Argentina. The SIB partner, expert in the functional annotation of human proteins, maintains the neXtProt knowledge base on human proteins and uses bioinformatics to predict the function of poorly characterized proteins. It has recently participated to a number of international studies aiming to catalog the sperm proteome in the framework of the HUPO Human Proteome Project. The IBYME partner is expert in human sperm physiology and will use antibodies that have been validated by the Human Protein Atlas (HPA) team to characterize the expression of the protein candidates in human sperm, and to evaluate their involvement in sperm fertilization. This study will improve the annotation of human proteins linked to fertility and may unravel new targets for the diagnosis and treatment of male infertility.