Human endometrial cell–conditioned medium enhances sperm chromatin integrity through HSPA2-containing uterosomes in vitro

Abstract

Sperm chromatin integrity is essential for successful fertilization and normal embryo development; however, a substantial proportion of infertile men exhibit abnormalities in sperm chromatin structure. Recent studies have shown that exosomes isolated from the conditioned medium of adipose tissue–derived mesenchymal stem cells may improve sperm chromatin abnormality following in vitro incubation, highlighting the potential of exosome-mediated mechanisms. Heat shock protein A2 (HSPA2) is a key regulator of genome remodeling during sperm chromatin maturation and has been identified in both the mouse endometrium and avian uterosomes. Accordingly, this study investigates whether human endometrial cell–conditioned medium (EC-CM) containing uterosomes (endometrium-derived exosomes) can improve sperm quality by targeting chromatin abnormalities. This study aimed to evaluate the presence of HSPA2 within uterosomes and, if present, to explore whether the transfer of uterosomal HSPA2 to sperm contributes to sperm chromatin remodeling. Our findings indicate that EC-CM contains uterosomes with HSPA2, and incubation of sperm with abnormal chromatin structure with EC-CM is associated with improved chromatin abnormality. These results suggest that bioactive molecules released by endometrial cells may contribute to the modulation of sperm chromatin quality and highlight a potential role in improving sperm function prior to assisted reproductive technologies.