ORIGINAL RESEARCH article
Front. Genet.
Sec. Computational Genomics
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1652519
Immune-Molecular Nexus in Reproductive Disorders: Mechanisms Linking POI and RSA
Provisionally accepted
- 1Zhenjiang Fourth People's Hospital, Jiangsu, China
- 2The Second People's Hospital of Lianyungang, Lianyungang, 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: Infertility remains a prevalent global health concern, with Premature Ovarian Insufficiency (POI) and Recurrent Spontaneous Abortion (RSA) being common causes of female infertility. Objective: This study aims to identify new central genes and potential therapeutic drugs for RSA and POI by integrating multi transcriptome data and machine learning algorithms. Methods: This study utilized RNA sequencing data from patients with POI and RSA to identify key hub genes associated with these diseases. The analysis involved machine learning algorithms, mcode and Cytoscape, revealing important hub genes. The comprehensive evaluation includes functional annotation, protein-protein interaction (PPI) network, transcription factor (TF) gene regulatory network, microRNA (miRNA) gene regulatory network. Genome enrichment analysis (GSEA) and immune infiltration studies elucidated the potential mechanism between POI and RSA. Drug target enrichment analysis highlighted promising therapeutic agents against RSA and POI. Validation of granulosa cells and endometrial tissue samples using quantitative real-time polymerase chain reaction (qRT-PCR) highlighted the importance of the identified hub genes. Results: This study identified a total of 6 hub genes—— CENPW, ENTPD3, FOXM1, GNAQ, LYPLA1, and PLA2G4A. Immunoassay revealed an increase in activated NK cells. Furthermore, significant differences were observed in the proportions of other immune cell types, such as resting memory CD4 T cells, compared to the control group. Significantly, these six genes participate in diverse metabolic pathways linked to RSA and POI, particularly in oxidative phosphorylation, ribosome processes, and steroid biosynthesis pathways. Additionally, ten potential drugs (Rifabutin, Methaneseleninic Acid, Carbamazepine, Dasatinib,,Troglitazone, Tamoxifen, Enterolactone, Anisomycin, Testosterone, 5-Fluorouracil) targeting key genes were identifed. Conclusions: Targeting these genes shows promise for preventing and treating both POI and RSA, providing crucial insights into addressing these complex conditions at molecular level.
Keywords: PREMATURE OVARIAN INSUFFICIENCY, Recurrent spontaneous abortion, Integrated transcriptomic analysis, machine learning, Drug target enrichment
Received: 28 Jun 2025; Accepted: 15 Sep 2025.
Copyright: © 2025 Chen, Zhu, Zhang, Zhang, Li, Liu and Dan. 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:
Xiaolan Zhu, Zhenjiang Fourth People's Hospital, Jiangsu, China
Xinyue Zhang, Zhenjiang Fourth People's Hospital, Jiangsu, China
Subo Zhang, The Second People's Hospital of Lianyungang, Lianyungang, 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.