INVITED REVIEW
Year : 2015  |  Volume : 17  |  Issue : 4  |  Page : 554-560

Negative biomarker based male fertility evaluation: Sperm phenotypes associated with molecular-level anomalies


1 Division of Animal Science and Departments of Obstetrics, Gynecology and Women's Health, University of Missouri, Columbia, Missouri, USA
2 Department of Human Genetics, McGill University, Quebec, Canada
3 Department of Biomedical and Molecular Sciences, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain
4 Queens University, Kingston, Ontario, Canada

Correspondence Address:
Peter Sutovsky
Division of Animal Science and Departments of Obstetrics, Gynecology and Women's Health, University of Missouri, Columbia, Missouri, USA

Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1008-682X.153847

Rights and Permissions

Biomarker-based sperm analysis elevates the treatment of human infertility and ameliorates reproductive performance in livestock. The negative biomarker-based approach focuses on proteins and ligands unique to defective spermatozoa, regardless of their morphological phenotype, lending itself to analysis by flow cytometry (FC). A prime example is the spermatid specific thioredoxin SPTRX3/TXNDC8, retained in the nuclear vacuoles and superfluous cytoplasm of defective human spermatozoa. Infertile couples with high semen SPTRX3 are less likely to conceive by assisted reproductive therapies (ART) and more prone to recurrent miscarriage while low SPTRX3 has been associated with multiple ART births. Ubiquitin, a small, proteolysis-promoting covalent posttranslational protein modifier is found on the surface of defective posttesticular spermatozoa and in the damaged protein aggregates, the aggresomes of spermiogenic origin. Semen ubiquitin content correlates negatively with fertility and conventional semen parameters, and with sperm binding of lectins LCA (Lens culinaris agglutinin; reveals altered sperm surface) and PNA (Arachis hypogaea/peanut agglutinin; reveals acrosomal malformation or damage). The Postacrosomal Sheath WWI Domain Binding Protein (PAWP), implicated in oocyte activation during fertilization, is ectopic or absent from defective human and animal spermatozoa. Consequently, FC-parameters of PAWP correlate with ART outcomes in infertile couples and with fertility in bulls. Assays based on the above biomarkers have been combined into multiplex FC semen screening protocols, and the surface expression of lectins and ubiquitin has been utilized to develop nanoparticle-based bull semen purification method validated by field artificial insemination trials. These advances go hand-in-hand with the innovation of FC-technology and genomics/proteomics-based biomarker discovery.


[FULL TEXT] [PDF]*
Print this article     Email this article
 Next article
 Previous article
 Table of Contents

 Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
 Citation Manager
 Access Statistics
 Reader Comments
 Email Alert *
 Add to My List *
 * Requires registration (Free)
 

 Article Access Statistics
    Viewed4312    
    Printed86    
    Emailed0    
    PDF Downloaded705    
    Comments [Add]    
    Cited by others 27    

Recommend this journal