Lipid imbalance and inflammatory oxylipin cascade at the maternal-fetal interface in recurrent spontaneous abortion
Hao Liu,
Huijia Chen,
Ting Han,
Xin Wang,
Jingcong Dai,
Xiaojia Yang,
ShanAn Chan,
Richard D. Cannon,
Yang Yang,
Hatem Mousa,
Shufang Chang,
Ruiqi Chang,
Ting-Li Han
Affiliations
Hao Liu
Department of Obstetrics and Gynaecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
Huijia Chen
The Center for Reproductive Medicine, Department of Obstetrics and Gynaecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
Ting Han
Department of Obstetrics and Gynaecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Obstetrics and Gynecology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
Xin Wang
State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, Chongqing, China
Jingcong Dai
Department of Obstetrics and Gynaecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
Xiaojia Yang
Department of Occupational and Environmental Hygiene, School of Public Health, Research Center for Medicine and Social Development, Innovation Center for Social Risk Governance in Health, Chongqing Medical University, Chongqing, China
ShanAn Chan
Agilent Technology, Inc, Taiwan, China
Richard D. Cannon
Department of Oral Sciences, Faculty of Dentistry, Sir John Walsh Research Institute, University of Otago, Dunedin, New Zealand
Yang Yang
Department of Obstetrics and Gynaecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Hatem Mousa
University of Leicester, NHS Trust, Leicester, UK
Shufang Chang
Department of Obstetrics and Gynaecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
Ruiqi Chang
The Center for Reproductive Medicine, Department of Obstetrics and Gynaecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China; Joint International Research Lab for Reproduction and Development, Ministry of Education, Chongqing, China; Reproduction and Stem Cell Therapy Research Center of Chongqing, Chongqing Medical University, Chongqing, China; Corresponding author. The Center for Reproductive Medicine, Department of Obstetrics and Gynaecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Ting-Li Han
Department of Obstetrics and Gynaecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China; Corresponding author.
Background: Recurrent spontaneous abortion (RSA) is intricately linked to metabolic dysregulation at the maternal-fetal interface during early gestation. Abnormal levels of essential fatty acids and downstream oxylipins in decidua and chorionic villi have been identified as potential risk factors for RSA. Oxylipins have been linked to excessive inflammation, which might disrupt maternal-fetal immune tolerance, potentially contributing to RSA. Nonetheless, the exact fatty acid-oxylipin metabolic pathway at the matrernal-fetal interface in RSA occurrence remains unknown. Therefore, this research aimed to explore the effect of essential fatty acids, their transport, and downstream oxylipins at the maternal-fetal interface on RSA pathogenesis. Methods: Plasma, chorionic villus, and decidual tissue samples from the first trimester were collected from healthy pregnant women undergoing elective pregnancy terminations, as well as from patients experiencing spontaneous abortion. The concentrations of essential fatty acids and their downstream oxylipins in the villi and decidua were quantified using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS). The expression of enzymes related to metabolic pathways was investigated by q-PCR. The ratios of M1/M2 macrophages were assessed by flow cytometry (FCM). Results: This study found elevated concentrations of omega-6 fatty acids, encompassing arachidonic acid (AA), linoleic acid (LA), and dihomo-gamma-linolenic acid (DGLA) in maternal plasma and chorionic villi, whereas lower concentrations were observed in the decidua, than in samples from normal pregnancies. Further analysis revealed that the transport of these fatty acids was dysregulated at the maternal-fetal interface in RSA women, possibly due to the aberrant expression of the fatty acid translocase (FAT/CD36). In addition, this study revealed that RSA patients displayed higher levels of downstream oxylipins, such as prostaglandin F2a (PGF2a), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) in chorionic villi and decidua. These compounds may contribute to M1 inflammatory macrophage polarization in RSA, thereby forming a highly inflammatory environment and influencing immunomodulation at the maternal-fetal interface. Conclusion: The study revealed alterations in omega-6 fatty acids, CD36 transport, and AA downstream oxylipins in RSA, which in turn promote M1 macrophage polarization. Thus, this research has established a foundation for identifying potential biomarkers for, and providing novel insights into, the diagnosis and pathophysiology of RSA.
