Experimental validation of seminal miR‐31‐5p as biomarker for azoospermia and evaluation of the effect of preanalytical variables

Abstract

Background and objectives: Predicting the origin of azoospermia with non-invasive biomarkers is clinically relevant for determining the chance of successful sperm retrieval from the testes before attempting ART. Here, the semen small extracellular vesicle (sEV) microRNA (miRNA) miR-31-5p-based biomarker test to distinguish obstructive (OA) from secretory azoospermia (SA) (previously described by our group) is validated for clinical use and additionally sample source [seminal sEVs vs total seminal plasma (SP)] as a preanalytical variable is considered to optimize the procedure. Results and discussion: Our results provide evidence that altered miR-31-5p expression can be determined both from EVs and from the whole SP to discriminate OA from SA azoospermic samples. Not only have we validated this miRNA-based molecular model as a clinically useful test for predicting the origin of azoospermia in a sample from azoospermic individuals, but additionally, and more interestingly for the clinicians, we have evidenced its usefulness for predicting the presence of spermatogenic failure in azoospermic patients with FSH values <10 IU/L as a sensitive and specific biomarker (AUC>0.88; p-value<0.006). This article is protected by copyright. All rights reserved. Keywords: Seminal plasma; azoospermia; extracellular vesicles; miRNA; non-invasive biomarker.