Protective effects of canthaxanthin-loaded seminal exosomes on the quality of human spermatozoa during cryopreservation

In contemporary times, sperm cryopreservation stands as the foremost and widely employed strategy for preserving male fertility, especially within assisted reproductive technology (ART) programs. This technique finds extensive application for preserving fertility in males undergoing chemotherapy, radiation therapy, severe oligospermia, ejaculatory failure, and conditions such as damaged testicles due to diabetes and autoimmune diseases [1,2]. The unique characteristics of spermatozoa, including high membrane fluidity and low water content (approximately 50 %), render them less susceptible to cryo-destructive effects compared to other cells [3]. However, despite these advantages, cryopreservation may cause detrimental alterations in the physical characteristics and biological role of spermatozoa, arising from factors such as ice crystal formation, dehydration, osmotic and thermal shock [4]. Notably, the freeze-thaw process is reported to significantly alter the structure and function of the mitochondrial membrane, leading to decreased sperm motility [5]. Furthermore, cryopreservation induces changes in mitochondrial membrane fluidity, impacting mitochondrial membrane potential (MMP), and consequent reactive oxygen species (ROS) production [6,7]. This, in turn, leads to harm to the membrane systems of spermatozoa and disruption of axoneme [5]. Sperm cryopreservation also diminishes antioxidant activity, rendering sperm more susceptible to ROS [8]. Elevated ROS levels and reduced antioxidant enzymes contribute to the release of apoptotic factors from mitochondria [9], leading to DNA fragmentation and activation of the cellular apoptosis pathway [10,11]. In light of these challenges, it is proposed that the addition of mitochondria-targeting antioxidants to the freezing medium could mitigate cryopreservation-induced damages [12,13]. Canthaxanthin (CAN), a carotenoid with antioxidant properties, has demonstrated protective effects in sperm cryopreservation by enhancing various parameters [14]. However, the limited bioavailability and water insolubility of CAN pose constraints on its use [15]. To address these limitations, the adoption of a drug delivery system becomes crucial. Semen-derived exosomes, with their endogenous and non-toxic characteristics, emerge as promising candidates for delivering antioxidants [16]. Exosomes (EXO), nanovesicles secreted by cells, provide a means for directly delivering targeted therapeutic cargo to the cytoplasm of cells [17,18]. Seminal exosomes, originating primarily from the prostate (prostasome) and epididymis (epididymosome), play crucial roles in sperm motility, capacitation, acrosome reaction, membrane fluidity, and protection against oxidative stress through antioxidant activities [19,20]. Recognizing the significance of sperm injuries during cryopreservation, this research aims to enhance canthaxanthin's bioavailability in sperm cryopreservation by loading it into seminal exosomes.

留言 (0)

沒有登入
gif