Extracellular vesicles (EVs), which contain various functional classes of vesicles, namely exosomes, microvesicles, and apoptotic bodies, represent the major nano-shuttle to transfer bioactive molecules from donor to recipient cells to facilitate cell-to-cell communication in the follicular, oviduct, and uterine microenvironments. In addition to transferring various molecular cargos in the form of miRNAs, mRNAs, proteins, lipids, and DNA molecules, the relative proportion of those molecular cargos in the reproductive fluids can be associated with the physiological and pathological condition of the host animal. Inside the follicle, EV-mediated circulation of miRNAs has been reported to be associated with the growth status of the enclosed oocytes, the metabolic status, and the advanced maternal aging of the animal. Importantly, EVs have the potential to protect their cargo molecules from extracellular degradation or modification while travelling to the recipient cells. This fact together with the enormous availability in almost all biological fluids and spent culture media make them attractive in the search for biomarkers of oocyte/embryo developmental competence, receptive maternal environment and a multitude of reproductive pathophysiological conditions. One of the key factors that have contributed to the lower efficiency of assisted reproductive technologies (ART) is the absence of several maternal in vivo factors in the ART procedures. For this, several studies have been conducted to supplement various components present in the follicular and oviductal fluids into the existing ART procedures and significant positive impacts have been observed in terms of embryo cleavage rate, blastocyst rate, resistance to stress, and survival after cryopreservation. The potential of EVs in shuttling protective messages against environmental and physiological stressors has been evidenced. The effective use of the EV-coupled molecular signals against stress-associated conditions has the potential to pave the path for the application of these protective signals against oxidative stress-associated pathological conditions including PCOS, ageing, and endometritis. In this review, we provide current knowledge and potential future use of EVs as remedies in reproductive pathophysiological conditions, mainly in follicular and oviductal microenvironments.
Background Among the various seasonal environmental changes, elevated ambient temperature during the summer season is a main cause of stress in dairy and beef cows, leading to impaired reproductive function and fertility. Follicular fluid extracellular vesicles (FF-EVs) play an important role in intrafollicular cellular communication by, in part, mediating the deleterious effects of heat stress (HS). Here we aimed to investigate the changes in FF-EV miRNA cargoes in beef cows in response to seasonal changes: summer (SUM) compared to the winter (WIN) season using high throughput sequencing of FF-EV-coupled miRNAs. In addition to their biological relevance, the potential mechanisms involved in the packaging and release of those miRNAs as a response to environmental HS were elucidated. Results Sequencing analysis revealed that an average of 6.6% of the EV-RNA mapped reads were annotated to bovine miRNAs. Interestingly, miR-148a, miR-99a-5p, miR-10b, and miR-143 were the top four miRNAs in both groups accounting for approximately 52 and 62% of the total miRNA sequence reads in the SUM and WIN groups, respectively. A group of 16 miRNAs was up-regulated and 8 miRNAs were down-regulated in the SUM compared to the WIN group. Five DE-miRNAs (miR-10a, miR-10b, miR-26a, let-7f, and miR-1246) were among the top 20 expressed miRNA lists. Sequence motif analysis revealed the appearance of two specific motifs in 13 out of the 16 upregulated miRNAs under HS conditions. Both motifs were found to be potentially bonded by specific RNA binding proteins including Y-box binding proteins (YBX1 and YBX2) and RBM42. Conclusion Our findings indicate that FF EV-coupled miRNA profile varies under seasonal changes. These miRNAs could be a good indicator of the cellular mechanism in mediating HS response and the potential interplay between miRNA motifs and RNA binding proteins can be one of the mechanisms governing the packaging and release of miRNAs via EVs to facilitate cellular survival.
Innumerable similarities in reproductive cyclicity and hormonal alterations highlight the considerable utility of the mare to study aspects of follicular dynamics and reproductive function in view of the largely constricted, human research subjects. The bi-directional communication between the growing oocyte and the surrounding somatic cells embodies the hallmark of mammalian follicular development, partially mediated by extracellular vesicles (EVs) encapsulated with microRNAs (miRNAs) and present in the follicular fluid (FF). Here, we aimed to decipher the dynamics of the miRNAs in EVs from equine FF aspirated in vivo during different stages of follicular development, namely, predeviation (PreDev; 18–20 mm), deviation (Dev; 22–25 mm), postdeviation (PostDev; 26–29 mm), preovulatory (PreOV; 30–35 mm), and impending ovulation (IMP; ∼40 mm). Approximately 176 known miRNAs were found in all groups with 144 mutually detected among all groups. Cluster analysis exhibited 15 different expression patterns during follicular development. Among these patterns, a group of 22 miRNAs (including miR-146b-5p, miR-140, and miR-143) exhibited a sharp reduction in expression from the PreDev until the PreOV stage. Another cluster of 23 miRNAs (including miR-106b, miR-199a-5p, and miR-125a-5p) exhibited a stable expression pattern at the PreDev stage until the PostDev stage, with a significant increase at the PreOV stage followed by a significant decrease at the IMP stage. In conclusion, this study provides greater insights into the stage-specific expression dynamics of FF EV-miRNAs during equine follicular development, which may propose novel approaches to improve ART and provide new biomarkers to facilitate the assessment of ovarian pathophysiological conditions.
Climate change-induced global warming results in rises in body temperatures above normal physiological levels (hyperthermia) with negative impacts on reproductive function in dairy and beef animals. Extracellular vesicles (EVs), commonly described as nano-sized, lipid-enclosed complexes, harnessed with a plethora of bioactive cargoes (RNAs, proteins, and lipids), are crucial to regulating processes like folliculogenesis and the initiation of different signaling pathways. The beneficial role of follicular fluid-derived EVs in inducing thermotolerance to oocytes during in vitro maturation (IVM) has been evidenced. Here we aimed to determine the capacity of in vitro cultured granulosa cell-derived EVs (GC-EVs) to modulate bovine oocytes’ thermotolerance to heat stress (HS) during IVM. Moreover, this study tested the hypothesis that EVs released from thermally stressed GCs (S-EVs) shuttle protective messages to provide protection against subsequent HS in bovine oocytes. For this, sub-populations of GC-EVs were generated from GCs subjected to 38.5°C (N-EVs) or 42°C (S-EVs) and supplemented to cumulus-oocyte complexes (COCs) matured in vitro at the normal physiological body temperature of the cow (38.5°C) or HS (41°C) conditions. Results indicate that S-EVs improve the survival of oocytes by reducing ROS accumulation, improving mitochondrial function, and suppressing the expression of stress-associated genes thereby reducing the severity of HS on oocytes. Moreover, our findings indicate a carryover impact from the addition of GC-EVs during oocyte maturation in the development to the blastocyst stage with enhanced viability.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.