ORIGINAL RESEARCH article

Front. Endocrinol.

Sec. Reproduction

Volume 16 - 2025 | doi: 10.3389/fendo.2025.1572388

The Impact of Different Ovarian Stimulation Protocols on the Expression Levels of GDF-9 and BMP-15 in Cumulus Cells of Follicles

Provisionally accepted
Lili  ChengLili Cheng1*Jie  ZhangJie Zhang2Dongxiu  LiDongxiu Li1Pengyu  XuPengyu Xu1Shan  LiuShan Liu2Ruijuan  GuoRuijuan Guo1Xue  WangXue Wang1Li  ZhangLi Zhang1
  • 1Third Hospital of Hebei Medical University, Shijiazhuang, China
  • 2Bethune International Peace Hospital, Shijiazhuang, Hebei Province, China

The final, formatted version of the article will be published soon.

Objective: To analyse the expression levels of the oocyte-secreted factors growth differentiation factor-9 (GDF-9) and bone morphogenetic protein-15 (BMP-15) in cumulus cells (CCs) under different controlled ovarian stimulation (COS) protocols and their association with oocyte maturity and embryo developmental potential.Methods: This study included 76 patients requiring intracytoplasmic sperm injection (ICSI) due to severe oligoasthenoteratozoospermia or previous ICSI treatment, resulting in the collection of 749 CC samples. Patients were divided into four groups based on COS protocols: short-acting luteal phase (14 patients, 168 CCs), long-acting follicular phase (21 patients, 189 CCs), micro-stimulation (12 patients, 86 CCs) and antagonist (29 patients, 306 CCs). mRNA was extracted from different cell stages, including oocytes, embryos and blastocysts, and real-time quantitative PCR was used to measure GDF-9 and BMP-15 expression. The expression levels of GDF-9 and BMP-15 were compared across protocols, and oocyte maturation, fertilisation, cleavage and blastocyst formation were assessed.Results: GDF-9 and BMP-15 levels were substantially higher in MⅡ oocytes than in MⅠ and GV oocytes and were also elevated in the normal fertilisation group, high-quality cleavage embryos and high-quality blastocysts. Growth differentiation factor-9 expression was higher in the short-acting luteal phase protocol than in the antagonist protocol, whereas BMP-15 expression was higher in both the short-acting luteal phase and long-acting follicular phase protocols compared with the micro-stimulation and antagonist groups.Conclusion: GDF-9 and BMP-15 are reliable indicators of oocyte developmental potential. The long-acting follicular phase and short-acting luteal phase protocols enhance oocyte maturity and embryo development, whereas the micro-stimulation and antagonist protocols appear less favourable.

Keywords: Oocyte-secreted factors, Granulosa Cells, Oocyte maturation, Controlled ovarian stimulation, Embryo development

Received: 07 Feb 2025; Accepted: 18 Apr 2025.

Copyright: © 2025 Cheng, Zhang, Li, Xu, Liu, Guo, Wang 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: Lili Cheng, Third Hospital of Hebei Medical University, Shijiazhuang, 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.

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