ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Molecular and Cellular Reproduction
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1518226
Optimizing In Vitro Maturation of Oocytes with Nitric Oxide Microbubble
Provisionally accepted
- 1Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- 2Zhejiang Zhuji People's Hospital, Zhuji, China
- 3Wenzhou Medical University, Wenzhou, Zhejiang Province, China
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Nitric oxide (NO) plays a pivotal role in female reproductive processes, yet its clinical translation is limited by its short half-life and rapid systemic clearance. In this study, we constructed lipid-based microbubbles (NO-MBs) via lyophilization to encapsulate and stabilize therapeutic NO gas, optimizing their parameters (particle count: 2.23×10 7 MBs/ml; diameter: 0.919±0.807 µm) for controlled release and prolonged circulation. Compared to conventional NO donors (e.g., SNP), NO-MBs demonstrated superior biosafety and efficacy in enhancing in vitro oocyte maturation. Specifically, NO-MBs significantly increased the maturation rate of mice immature oocytes (72.00% vs. 57.77% in controls) while improving oocyte quality, as evidenced by elevated Ca 2+ levels, mitochondrial membrane potential (MMP), and reduced intracellular ROS. In vivo, NO-MBs enhanced oocyte retrieval and fertilization rates while reducing blastocyst cell apoptosis. Mechanistically, NO-MBs uniquely activated phosphorylated ERK, suggesting ERK pathway involvement in oocyte maturation. These findings highlight NO-MBs as a novel, clinically relevant strategy for targeted NO delivery in reproductive medicine, offering potential applications in assisted reproductive technologies (ART) to improve oocyte quality and developmental outcomes. Figure 1. Schematic illustration of Nitric Oxide-loaded microbubbles (NO-MBs) preparation via lyophilization and their role in optimizing oocyte IVM outcomes.
Keywords: Nitric Oxide, Lipid microbubbles, Gas drug delivery, oocyte, In vitro maturation
Received: 07 Nov 2024; Accepted: 31 Mar 2025.
Copyright: © 2025 Qiu, Xu, Lin, Wang, Zhang, Liu, Zhao, Zhao and Xi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Haitao Xi, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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