ESA-SRB-AOTA 2019

Proteomic markers in seminal plasma as a non-invasive alternative for the differential diagnosis of azoospermia (#223)

Raouda Sgaier 1 2 3 , Daniela Fietz 3 , Martin Bergmann 3 , Liza O'Donnell 1 , Peter Stanton 1 , Laura Dagley 4 , Andrew I Webb 4 , Hans-Christian Schuppe 2 , Adrian Pilatz 2 , Thorsten Diemer 2
  1. Hudson Institute for Medical Research, Clayton, VIC, Australia
  2. Department of Urology, Pediatric Urology and Andrology, Justus Liebig University, Giessen, Hessen, Germany
  3. Department of Veterinary Anatomy, Histology and Embryology, Justus Liebig University, Giessen, Hessen, Germany
  4. The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia

Infertility affects approximately 15% of couples of reproductive age with almost equivalent male and female contribution. Azoospermia, characterized by non-measurable levels of sperm in semen, is responsible for 5-20% of male infertility cases. With the advent of ARTs, an exact diagnosis of male factor infertility is of prime importance in infertility management. The aim of this study was to discover biomarkers for non-invasive differential diagnosis of azoospermia. Using label-free LC-MS/MS, we compared proteomic profiles of seminal plasma from fertile men (healthy controls, HC) and men diagnosed with three different forms of azoospermia: obstructive (OA), hypospermatogenesis (HS) and Sertoli cell only syndrome (SCO) (all groups n=8). Proteins significantly down-regulated in SCO and OA compared to the control included testis-specific LDHC (FCHC/OA= 5.24; p=0.02, FCHC/SCO= 5.38; p=0.01) and testis-enhanced TSN (FCHC/OA= 2.96; p=0.04, FCHC/SCO= 3.24; p=0.02) and HSP90AA1 (FCHC/OA= 2.25; p=0.04, FCHC/SCO= 2.29; p=0.02). This decrease is caused by two distinct mechanisms: the physical obstruction of the male reproductive tract in OA, and testicular failure in SCO. Results also showed a lower abundance of a number of epididymal-enriched proteins in seminal plasma from the OA group compared to the non-obstructive azoospermia (SCO, HS) and control groups. ELSPBP1 (FCHC/OA= 9.78, p=0.02), and MGAM (FCHC/OA= 6.27, p=0.04) were selected as candidate markers of vas deferens obstruction. Quantitation of these proteins in seminal plasma using antibody-based assays will be undertaken as a primary marker validation step. Further analysis of sample distribution demonstrated the potential of seminal plasma proteomics to distinguish between hypospermatogenesis and SCO, and to classify OA cases according to the site of obstruction. Developing tools for the accurate, non-invasive diagnosis of azoospermia can inform clinical decisions and help speed up infertility treatment. Proteomic markers measured in seminal plasma, in combination with conventional clinical tests, can offer a good alternative to testicular biopsy.