ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Molecular and Cellular Reproduction
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1647476
This article is part of the Research TopicThe Fertilization Success from the Oocyte's Perspective, Volume IIView all 5 articles
Aquaporin 2 is Differentially Expressed in Granulosa Cells of Various Stages of Human Follicles and is Regulated by Luteinizing Hormone
Provisionally accepted
- 1The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- 2Shenzhen Maternity and Child Healthcare Hospital,Women and Children's Medical Center，Southern Medical University, Shenzhen, Guangdong Province, China
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Several aquaporins (AQPs) are involved in the influx of water to form follicular fluid, and AQP2 may play a crucial role in follicular growth. However, the specific roles of Aquaporin (AQP) 2 and AQP6 in granulosa cells (GCs) during follicular fluid (FF) formation, as well as their relationship with gonadotropins (Gn), remain unclear. Our research revealed that AQP2 levels in luteinized GCs (LGCs) increased as follicles grew larger after luteinization, whereas the levels decreased as follicles progressed from primordial to antral stages.To elucidate these mechanisms, LGCs were treated with varying concentrations of folliclestimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2). We found that LH, but not E2, significantly induced AQP2 expression in LGCs, suggesting that mechanisms other than the direct function of E2 are involved. To further investigate the underlying mechanisms, LGCs were cultured with LH, db-cAMP (a cAMP analog), or forskolin (an adenylate cyclase activator).Forskolin was found to have a comparable effect on AQP2 expression to that of LH. To preliminarily determine whether there is crosstalk between the Gn/cAMP signaling pathway and the MAPK signaling cascade, H89 (a PKA inhibitor) or PD98059 (an ERK1/2 signaling inhibitor) was added in the presence of LH. The results showed that PD98059 inhibited the phosphorylation of ERK1/2, suggesting potential crosstalk between these pathways.To our knowledge, this is the first study to explore the mechanisms by which AQP2 influences follicular growth and FF formation. Our findings provide new insights into the ovarian microenvironment and follicular development, potentially offering therapeutic targets for follicle growth disorders.
Keywords: Aquaporin 2, Follicular Fluid, Follicular growth, Luteinization, Granulosa Cells, Theca Cells
Received: 15 Jun 2025; Accepted: 31 Jul 2025.
Copyright: © 2025 Zheng, Tan, Chen, Liu, Wen, Zhou and Li. 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: Yubin Li, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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