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  3. Mitochondrial genetic landscape and its correlation with immune cell infiltration in preeclampsia: Insights from bioinformatics

Mitochondrial genetic landscape and its correlation with immune cell infiltration in preeclampsia: Insights from bioinformatics

  • J Reprod Immunol. 2025 Jun:169:104527. doi: 10.1016/j.jri.2025.104527.
Xunjia Ye 1,  Jieying Yu 2,  Youyuan Zhuo 2,  Anlu Yong 2,  Jiachun Wei 3,  Ruiman Li 4,  Shuo Wan 5,  Guang Wang 6,  Xuesong Yang 7
Affiliations

Affiliations

  • 1 Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Guangdong Second Provincial General Hospital, School of Medicine, Jinan University, Guangzhou 510317, China; International Joint Laboratory for Embryonic Development & Prenatal Medicine, Division of Histology and Embryology, School of Medicine, Jinan University, Guangzhou 510632, China.
  • 2 International Joint Laboratory for Embryonic Development & Prenatal Medicine, Division of Histology and Embryology, School of Medicine, Jinan University, Guangzhou 510632, China.
  • 3 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510632, China.
  • 4 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510632, China. Electronic address: hqyylrm@126.com.
  • 5 International Joint Laboratory for Embryonic Development & Prenatal Medicine, Division of Histology and Embryology, School of Medicine, Jinan University, Guangzhou 510632, China; Key Laboratory for Regenerative Medicine of the Ministry of Education, Jinan University, Guangzhou 510632, China. Electronic address: shuowan6@jnu.edu.cn.
  • 6 Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Guangdong Second Provincial General Hospital, School of Medicine, Jinan University, Guangzhou 510317, China; International Joint Laboratory for Embryonic Development & Prenatal Medicine, Division of Histology and Embryology, School of Medicine, Jinan University, Guangzhou 510632, China; Key Laboratory for Regenerative Medicine of the Ministry of Education, Jinan University, Guangzhou 510632, China. Electronic address: t_wangguang@jnu.edu.cn.
  • 7 International Joint Laboratory for Embryonic Development & Prenatal Medicine, Division of Histology and Embryology, School of Medicine, Jinan University, Guangzhou 510632, China; Key Laboratory for Regenerative Medicine of the Ministry of Education, Jinan University, Guangzhou 510632, China; International School, Guangzhou Huali College, Zengcheng, Guangzhou 511325, China. Electronic address: yang_xuesong@126.com.
PMID: 40203595 DOI: 10.1016/j.jri.2025.104527
Abstract

Background: Preeclampsia (PE), a hypertensive pregnancy disorder, remains a leading cause of maternal and perinatal morbidity and mortality. Mitochondria-related placental metabolic dysfunction is implicated in PE, but its mechanistic role is unclear. This study aimed to identify mitochondria-related genes (MRGs) and their possible regulatory mechanisms in PE.

Methods: Differentially expressed mitochondria-related genes (MRGs) of PE were identified from Gene Expression Omnibus (GEO) dataset GSE114691 and GSE190971. LASSO regression analysis was used to screen key MRGs. Datasets GSE75010 and GSE25906 were used to validate the efficiency of the MRGs predictive model via receiver operating characteristic (ROC) curve analysis. Gene set enrichment analysis (GSEA) was conducted to verify underlying biological pathways in PE. Furthermore, we investigated the correlation analysis of MRGs and immune cell infiltration, as well as the association between the MRGs and clinical features. Single-cell Sequencing analysis and immunofluorescence staining were used to verify the expression of critical gene in the placenta.

Results: Five hub MRGs (MOCS1, CYP11A1, GATM, SFXN3, and BCL2L11) showed high diagnostic accuracy for PE and correlated with immune cell infiltration. CYP11A1 was further associated with Hemolysis, Elevated Liver Enzymes, Low platelets (HELLP) syndrome and predominantly expressed in extravillous trophoblasts, with upregulated expression in PE placenta.

Conclusion: The interaction between MRGs with the immune microenvironment might be vital in the development of PE. Among 5 hub MRGs, CYP11A1 might be a potential biomarker of HELLP syndrome. These findings provide novel insights into the underlying pathophysiology of PE and the discovery of new therapeutic targets.

Keywords

Bioinformatics analysis; Immune infiltration; Lasso regression; Mitochondria-related genes; Preeclampsia.

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