Diagnosis of infertility caused by sperm centriole dysfunction

Description:

Project ID D2020-37

Background
Couples struggling with infertility have the option of trying to expand their families with assisted reproductive technology (ART), such as in vitro fertilization. However, ART comes at a high cost and is only successful in about half of cases in the United States. Prior to electing ART, a couple’s fertility is assessed, including conventional parameters of sperm motility, morphology, and concentration. However, they still cannot explain a quarter of all worldwide infertility cases and their predictive value for pregnancy success is controversial. Newer test methods assess internal components, such as DNA, chromatin and centrioles. The important role of the centrioles in sperm morphology and movement pre-fertilization is well demonstrated and widely accepted. Mounting evidence suggest also that sperm centriole are essential for embryo development post fertilization. Several assays to study human sperm centrioles are available.  However, the associated technology is either laborious, only quantitative in nature, or not sufficiently specific to centrioles. Therefore, there is a need for a convenient way to assess centriole quality and predict the effectiveness of ART for a particular couple.

Invention Description
The Avidor-Reiss Lab recently reported that centrioles from male germ cells undergo a unique “centriole remodeling” during maturation into spermatozoa, which results in sperm centrioles having distinct, atypical characteristics. Using centriolar biomarkers and location-based Fluorescence-Based Ratiometric Analysis of Centrioles (FRAC), the investigators developed a predictive fertility assessment of the quality of both sperm centrioles and the axoneme. The calculated mean ratios of the patient sample can then be compared to a reference mean ratio; the implication of infertility due to centriole quality is suspected when a sample falls outside of the normal range.

Applications

  • Diagnose male infertility based on sperm centriole dysfunction
  • Helping doctors and patients understand the likelihood of success of ART treatments
  • Robust and convenient assay for research of centriole quality
  • Domestic animal reproduction

Advantages

  • Can be used in a routine clinical environment. 
  • High throughput is possible
  • Slide staining, imaging, and FRAC quantification can become automated to analyze the images in a streamlined process or sold as a kit for manual processing  
  • Highly novel; Takes into account the recently described atypical centrioles

IP Status:                           Patent Pending

Publications:                    

  1. Turner, K., Fishman, E.L., Asadullah, M., et al. Quantification Of Sperm Centriole Quality. Manuscript in preparation.
  2. Fishman, E.L., Jo, K., Nguyen, Q.P.H. et al.  A Novel Atypical Sperm Centriole is Functional During Human Fertilization. Nat Commun 9, 2210 (2018).
Patent Information:
Category(s):
Diagnostics
Animal Health
For Information, Contact:
Katherine Pollard
Licensing Associate
The University of Toledo
419-530-6228
katherine.pollard@utoledo.edu
Inventors:
Tomer Avidor-Reiss
Emily Fishman
Katrina Turner
Keywords:
Centriole
FRAC
Infertility
Sperm