BPDE (benzo(a)pyren-7,8-dihydrodiol-9,10-epoxide), a metabolite of environmental carcinogenic BaP, weakens the migration and invasion of human villous trophoblast cells and may further induce miscarriage. However, the underlying mechanisms remain largely unknown. In this study, we identified that in trophoblast Swan 71 and HTR-8/SVneo cells, miR-hz02 upregulates the level of lnc-HZ02, which inhibits the expression of an RNA-binding protein HuR. HuR could interact with FAK mRNA and promote its mRNA stability, thus upregulating the FAK level and the FAK/SRC/PI3K/AKT pathway, and finally maintaining the normal migration and invasion of trophoblast cells. If trophoblast cells are exposed to BPDE, both miR-hz02 and lnc-HZ02 are upregulated, which reduce the level of HuR, weaken the interactions of HuR with FAK mRNA, downregulate FAK level and the FAK/SRC/PI3K/AKT pathway, and finally inhibit cell migration and invasion. This study provides a novel scientific understanding of the dysfunctions of human trophoblast cells.
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http://dx.doi.org/10.1002/jbt.22757 | DOI Listing |
Sci Rep
December 2024
Laboratory of Molecular and Cellular Immunology, Institute of Molecular Biology NAS RA, 7 Hasratyan Str., Yerevan, 0014, Armenia.
Antiphospholipid syndrome (APS) is associated with recurrent pregnancy morbidity, yet the underlying mechanisms remain elusive. We performed multifaceted characterization of the biological and transcriptomic signatures of mouse placenta and uterine natural killer (uNK) cells in APS. Histological analysis of APS placentas unveiled placental abnormalities, including disturbed angiogenesis, occasional necrotic areas, fibrin deposition, and nucleated red blood cell enrichment.
View Article and Find Full Text PDFRev Med Interne
December 2024
Service de médecine interne et inflammation, département inflammation-immunopathologie-biothérapie (DMU I3), CEREMAIAA, hôpital Saint-Antoine, AP-HP, Sorbonne université, Paris, France.
Hydroxychloroquine (HCQ), a synthetic antimalarial, is recognized for its immunomodulatory, anti-inflammatory and vascular-protective effects. In 20-30% of cases of primary obstetrical antiphospholipid syndrome (APS), the combination of antiplatelet aggregation and prophylactic anticoagulation fails to prevent obstetrical complications, a situation referred to as refractory obstetrical APS. This is partly due to the pro-inflammatory effects of antiphospholipid antibodies (aPL) binding to decidual and trophoblastic cells, which compromise embryonic implantation and placentation.
View Article and Find Full Text PDFHypertens Pregnancy
December 2025
School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia.
Preeclampsia is a complex condition characterized by elevated blood pressure and organ damage involving kidneys or liver, resulting in significant morbidity and mortality for both the mother and the fetus. Increasing evidence suggests that oxidative stress, often caused by mitochondrial dysfunction within fetal trophoblast cells may play a major role in the development and progression of preeclampsia. Oxidative stress occurs as a result of an imbalance between the production of reactive oxygen species (ROS) and the capacity of antioxidant defenses, which can lead to placental cellular damage and endothelial cell dysfunction.
View Article and Find Full Text PDFCell Mol Life Sci
December 2024
The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 910# Hengshan Road, Shanghai, China.
Assisted reproductive technology (ART) pregnancies present a higher risk of singleton preterm birth than natural pregnancies, but the underlying molecular mechanism remains largely unknown. RNA mA modification is a key epigenetic mechanism regulating cellular function, but the role of mA modification, especially its "reader" YTHDC1, in preterm delivery remains undefined. To delineate the role and epigenetic mechanism of mA modification in ART preterm delivery, the effects of YTHDC1 on trophoblastic function were evaluated by CCK-8, EdU, Transwell, and flow cytometry analyses post its overexpression or knockdown.
View Article and Find Full Text PDFMol Med
December 2024
Department of Obstetrics, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, No.123, Tianfeixiang, Mochou Rd, Nanjing, 210004, China.
Background: Preeclampsia (PE) is a serious pregnancy complication associated with impaired trophoblast function. Integrin β3 (ITGB3) is a cell adhesion molecule that plays a role in cell movement. The objective of this study was to identify the biological function and expression level of ITGB3 in PE.
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