Extracellular vesicle-based regenerative strategies for male infertility and erectile dysfunction: Molecular mechanisms, preclinical evidence, and translational challenges.

Authors

Lida Aslanian-Kalkhoran, Majid Ebrahimi-Warkiani, Ali Hasanzadeh, Mohammad Hojjat-Farsangi, Maryam Ashourpour, Elham Badihi, Farshid Afandideh, Mehdi Yousefi

Published in

Experimental and molecular pathology. Volume 148. Pages 105100. Nov 14, 2026. Epub Nov 14, 2026.

Abstract

Extracellular vesicles (EVs) are membrane contained vesicles of nano size that transport cargo such proteins, lipids, and microRNAs (miRNAs) for interaction between cells. Naturally released EVs and their cargos have been implicated in the control of male reproductive physiology that includes spermatogenesis, testicular homeostasis, and erectile function. In addition to their physiological activities, compounds related to EVs have been proposed as possible biomarkers for male reproductive disorders. Administered EV preparations, especially those produced from stem cells, have been explored as prospective cell-free restorative therapies for male infertility and erectile dysfunction (ED). Recent research has shown that stem cell-derived EVs can promote tissue healing via anti-inflammatory, anti-apoptotic, pro-angiogenic, and immunomodulatory processes. Preclinical and experimental investigations indicate that these EV formulations might help improve spermatogenic and testicular results while facilitating neurovascular restoration and erectile recuperation; however, therapeutic effectiveness has primarily been shown in animal studies. Furthermore, the advances in EV engineering and biomaterial-based delivery strategies may increase their therapeutic potential through elevated targeting efficiency, cargo loading and regulated release. This review highlights current evidence on EV biology, potential as biomarkers, regenerative mechanisms, and therapeutic uses in male infertility and ED. A literature search was first undertaken in February 2025 on PubMed/MEDLINE, Scopus, and Web of Science and updated until September 16, 2026, focusing on papers dealing with EVs, male infertility, spermatogenesis, ED, biomarkers, and regenerative applications. The review also points to the main challenges that are limiting clinical translation, such as EV heterogeneity, large-scale production, standardization, characterization, delivery approaches, and long-term safety. Although EV-based interventions represent a promising cell-free regenerative strategy, clinical translation will require standardized nomenclature, manufacturing, characterization, potency testing, dosing, delivery, and long-term safety evaluation.

PMID:
43033568
Bibliographic data and abstract were imported from PubMed on 15 Nov 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.