ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Reproduction
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1627679
NADH Supplementation Improves Human Oocyte Maturation and Developmental Competence of Resulting Embryos in Controlled Ovarian Hyperstimulation Cycles: A Pilot Study Implicating the CDK2/GAS6 Signaling Pathway
Provisionally accepted
Qiqi Zhang
Han Yang
Dandan YangHedong LuMin XiongLanxin XieYongqi FanKuanjian ZhangChao ZhangTingting YeDing DingWeiwei Zou
Dongmei JiBeili ChenQiushuang Wang*
Huijuan Zou*
Zhiguo Zhang*- First Affiliated Hospital of Anhui Medical University, Hefei, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background Mitochondrial dysfunction in immature oocytes remains a critical barrier to successful in vitro maturation (IVM), particularly in cases of diminished ovarian reserve. While NAD⁺ precursors are extensively studied, the direct impact of NADH -the reduced form central to electron transport -on human oocyte maturation remains unexplored.Methods Discarded GV/MⅠ oocytes from controlled ovarian hyperstimulation (COH) cycles were randomized to IVM media supplemented with NADH (10 -8 -10 -4 M). The optimal concentration (10 -6 M) was determined by embryonic development. Mechanistic analyses included: mitochondrial phenotyping, single-cell RNA sequencing (scRNA-seq) and intervention experiments.Results NADH boosted maturation rates by 26.31% and blastocyst rates by 23.4% versus controls. Mitochondrial indices surged (ATP, mitochondrial membrane potential, glutathione, all P < 0.05), accompanied by ROS reduction. scRNA-seq and immunofluorescence results revealed NADH upregulated CDK2 and GAS6 genes. CDK2 inhibition suppressed maturation (5.13%), while NADH co-treatment partially restored rates (34.21%) after 24 hours. Exogenous GAS6 enhanced blastocyst formation by 44.44%.This pilot study demonstrates that NADH, as a mitochondrial bioenergetic enhancer, ameliorates Human oocytes maturation and subsequent embryonic development, with this promotive effect appearing to be associated with upregulation of CDK2 and GAS6.
Keywords: In vitro maturation, Nicotinamide adenine dinucleotide, immature human oocyte, maturation, Embryonic Development
Received: 13 May 2025; Accepted: 15 Aug 2025.
Copyright: © 2025 Zhang, Yang, Yang, Lu, Xiong, Xie, Fan, Zhang, Zhang, Ye, Ding, Zou, Ji, Chen, Wang, Zou and Zhang. 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:
Qiushuang Wang, First Affiliated Hospital of Anhui Medical University, Hefei, China
Huijuan Zou, First Affiliated Hospital of Anhui Medical University, Hefei, China
Zhiguo Zhang, First Affiliated Hospital of Anhui Medical University, Hefei, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.