2. Academic Validation
  3. Multi-omics analysis reveals steroid hormone biosynthesis as a key pathway in advanced maternal age threatened abortion†

Multi-omics analysis reveals steroid hormone biosynthesis as a key pathway in advanced maternal age threatened abortion†

  • Biol Reprod. 2026 Jun 15;114(6):2009-2022. doi: 10.1093/biolre/ioag045.
Xia Liu 1,  Tianjiao Liu 2,  Xuemei Zou 1,  Aolei Lin 3,  Cheng Chen 4,  Huan Yang 5,  Min Xia 1,  Mei Luo 1,  Xiaoyan Chen 1,  Junjie Deng 6,  Zhi Chen 1
Affiliations

Affiliations

  • 1 Department of Gynecology, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, China.
  • 2 Department of Gynecology, Chengdu Women's and Children's Central Hospital University of Electronic Science and Technology of China, Chengdu 611731, China.
  • 3 Department of Neurology, Tianjin Medical University General Hospital, Tianjin 300052, China.
  • 4 Department of Gynecology and Obstetrics, Chongqing General Hospital, Chongqing 401147, China.
  • 5 Department of Obstetrics, Chongqing University Three Gorges Hospital, Chongqing 401500, China.
  • 6 College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China.
PMID: 41757494 DOI: 10.1093/biolre/ioag045
Abstract

Advanced maternal age (≥35 years) is increasingly common and associated with a higher risk of threatened abortion, yet its molecular basis remains unclear. To elucidate the underlying mechanisms of advanced maternal age-related threatened abortion (AMA-TA) by integrating metabolomics and transcriptomics. Untargeted serum metabolomics was performed in nine AMA-TA patients and seven age-matched healthy pregnant women. An AMA-TA mouse model was established using mifepristone (4 mg/kg) to assess embryo resorption, placental morphology, and serum hormone levels. Serum metabolomics and placental transcriptomic profiling (RNA-seq) were then conducted in AMA-TA mice to characterize metabolic and gene expression alterations. Cross-species and multi-omics integration was performed using HomoloGene and MetaboAnalyst 5.0. Key genes were validated by real-time quantitative polymerase chain reaction. Human serum metabolomics revealed the differential metabolites were mainly enriched in steroid hormone biosynthesis, lipid metabolism, and amino-acid metabolism. The AMA-TA model showed higher embryo resorption, abnormal placental architecture, and reduced progesterone and chorionic gonadotropin. RNA-seq revealed 111 up- and 1337 downregulated genes enriched in 68 pathways. Consistently, serum metabolomics in AMA-TA mice also showed significant metabolic disturbances, prominently involving steroid hormone biosynthesis. Integrated analysis converged on steroid hormone biosynthesis as a shared key dysregulated pathway. Real-time quantitative polymerase chain reaction further confirmed aberrant expression of steroid metabolism-related genes, including upregulation of Akr1d1 and UGT family genes. Disruption of steroid hormone biosynthesis represents central molecular feature of AMA-TA. Integrated multi-omics analysis offers mechanistic insight and supports the development of biomarkers and therapeutic targets for AMA-TA.

Keywords

advanced maternal age; steroid biosynthesis; threatened abortion; transcriptomics; untargeted metabolomics.

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