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MiR-3074-5p Regulates Trophoblasts Function via EIF2S1/GDF15 Pathway in Recurrent Miscarriage
Jia-Xin Shi1, Long Yang1, Jie Gan1
1Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Medical School, Fudan University, Shanghai, 200237, China.
Reproductive Sciences (Thousand Oaks, Calif.)
|December 27, 2023
Summary
MicroRNA-3074-5p dysregulates extravillous trophoblast function by reducing GDF15, potentially causing recurrent miscarriages. This pathway involves targeting EIF2S1, impacting trophoblast invasion and implantation.
Area of Science:
- Reproductive Biology
- Molecular Endocrinology
- Genetics
Background:
- Extravillous trophoblast (EVT) dysfunction is linked to early pregnancy failure.
- Recurrent miscarriage (RM) is associated with altered microRNA and growth differentiation factor 15 (GDF15) levels.
- Previous findings indicated miR-3074-5p enhances EVT apoptosis and reduces invasion.
Purpose of the Study:
- To elucidate the role of the miR-3074-5p/GDF15 pathway in regulating EVT function.
- To investigate the regulatory mechanism between miR-3074-5p, EIF2S1, and GDF15 in EVTs.
Main Methods:
- Quantitative analysis of miR-3074-5p, GDF15, and EIF2S1 expression in villus samples from RM patients.
- In vitro studies using HTR8/SVneo cells to assess the impact of miR-3074-5p and GDF15 manipulation on EVT proliferation, migration, and invasion.
- Luciferase reporter assays to confirm direct targeting of EIF2S1 by miR-3074-5p.
Main Results:
- Villus GDF15 and EIF2S1 expression were significantly decreased in RM patients.
- miR-3074-5p directly targets EIF2S1, leading to reduced GDF15 production.
- Knockdown of GDF15 inhibited HTR8/SVneo cell proliferation, migration, and invasion; effects reversed by EIF2S1 overexpression or GDF15 treatment.
Conclusions:
- miR-3074-5p reduces GDF15 production by inhibiting EIF2S1 expression in EVTs.
- Deficiency in GDF15 function, mediated by this pathway, may contribute to early pregnancy loss by impairing EVT proliferation and invasion.
