ArticleCell proliferation2023
Insufficient GDF15 expression predisposes women to unexplained recurrent pregnancy loss by impairing extravillous trophoblast invasion.
Article in Cell proliferation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Long-term follow-up of a phase 1/2 trial of anti-GDF-15 antibody visugromab plus anti-PD-1 antibody nivolumab in anti-PD-1/-L1 relapsed/refractory solid tumors.Journal of hematology & oncology · 2026Trial
- EVT-Derived Migrasomes Provide Mechanistic Insights Into Antiphospholipid Syndrome-Associated Recurrent Miscarriage.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026Article
- Early pregnancy biomarkers of inflammation and metabolic regulation in polycystic ovary syndrome.The Journal of clinical endocrinology and metabolism · 2026Article
- Role of the trophoblastic BMP7-TGM2 axis in the pathogenesis and prevention of preeclampsia.Cell death & disease · 2026Article
- Functional characterization of the GWAS lead SNP rs888663 and effects of GDF15 SNPs on GDF15 levels in gestational hypertension and preeclampsia.Molecular biology reports · 2026Article
- Metabolic control of feto-placental development and pregnancy outcomes.Nature reviews. Endocrinology · 2026Review
- Prevalence and sociodemographic factors associated with hyperemesis gravidarum in pregnant women in European Arctic Russia, 2006-2018.BMC pregnancy and childbirth · 2026Article
- Asprosin activates multiple placental pathwaysMolecular medicine reports · 2025Article
- Metabolic Messenger: growth differentiation factor 15.Nature metabolism · 2025Review
- Fluorescent, pH, and UCST Responsive Polymer Nanomaterials for Treatment of Recurrent Miscarriage.Journal of fluorescence · 2025Article
- The BMP Signaling Pathway: Bridging Maternal-Fetal Crosstalk in Early Pregnancy.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- Melatonin affects trophoblast epithelial-to-mesenchymal transition and oxidative damage resistance by modulating GDF15 expression to promote embryo implantation.Communications biology · 2025Article
- Proximate and ultimate causes of pregnancy sickness.Evolution, medicine, and public health · 2025Review
- Basic Research Advances in China on Embryo Implantation, Placentation, and Parturition.Maternal-fetal medicine (Wolters Kluwer Health, Inc.) · 2024Article
- Re-examining the adaptive function of nausea and vomiting in pregnancy.Evolution, medicine, and public health · 2024Article
- Nausea, vomiting and conflict in pregnancy: The adaptive significance of Growth-Differentiation Factor 15.Evolution, medicine, and public health · 2024Article
- Insufficient GDF15 expression predisposes women to unexplained recurrent pregnancy loss by impairing extravillous trophoblast invasion.Cell proliferation · 2023Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Insufficient extravillous trophoblast (EVT) invasion during early placentation has been shown to contribute to recurrent pregnancy loss (RPL). However, the regulatory factors involved and their involvement in RPL pathogenesis remain unknown. Here, we found aberrantly decreased growth differentiation factor 15 (GDF15) levels in both first-trimester villous and serum samples of unexplained recurrent pregnancy loss (URPL) patients as compared with normal pregnancies. Moreover, GDF15 knockdown significantly reduced the invasiveness of both HTR-8/SVneo cells and primary human EVT cells and suppressed the Jagged-1 (JAG1)/NOTCH3/HES1 pathway activity, and JAG1 overexpression rescued the invasion phenotype of the GDF15 knockdown cells. Induction of a lipopolysaccharide-induced abortion model in mice resulted in significantly reduced GDF15 level in the placenta and serum, as well as increased rates of embryonic resorption, and these effects were reversed by administration of recombinant GDF15. Our study thus demonstrates that insufficient GDF15 level at the first-trimester maternal-foetal interface contribute to the pathogenesis of URPL by impairing EVT invasion and suppressing JAG1/NOTCH3/HES1 pathway activity, and suggests that supplementation with GDF15 could benefit early pregnancy maintenance and reduce the risk of early pregnancy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.