Study on the Mechanism of Inhibiting Trophoblast Invasion via the LAMA3-PI3K/Akt Pathway in Hyperandrogenic States of Advanced Maternal Age
10.11969/j.issn.1673-548X.2025.07.011
- VernacularTitle:高龄孕妇高雄激素状态通过LAMA3-PI3K/Akt通路抑制滋养细胞侵袭的机制研究
- Author:
Xuelei WU
1
;
Fengying LU
;
Bin YU
Author Information
1. 210000 南京医科大学;213003 南京医科大学附属常州市妇幼保健院遗传科
- Publication Type:Journal Article
- Keywords:
Advanced maternal age;
Placenta;
Androgens;
Laminin;
PI3K signaling pathway
- From:
Journal of Medical Research
2025;54(7):54-59,65
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the mechanism by which hyperandrogenic states induce preeclampsia in advanced maternal age through the LAMA3-PI3K/Akt pathway and assess its effects on the invasion and migration abilities of human trophoblast cells.Methods Human trophoblast cells were stimulated with dihydrotestosterone(DHT),followed by RNA sequencing(RNA-Seq)to identify differen-tially expressed genes,with gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)analysis revealing LAM A3 as a key molecule.The mRNA and protein expression levels of LAMA3 were detected using real-time quantitative PCR(RT-qPCR)and Western blot.LAMA3-overexpressing human trophoblast cells were obtained by plasmid transfection.The invasion ability was assessed using the Matrigel-based Transwell assay,and the migration ability was evaluated by the scratch assay.Results DHT stimulation sig-nificantly inhibited the invasion and migration abilities of trophoblast cells.RNA-Seq analysis revealed that LAM A3 might be a key mole-cule involved,and further Western blot and RT-qPCR analyses showed that the protein and mRNA expression of LAM A3 in the placenta of advanced maternal age pregnancies were significantly higher than in normal pregnancies and consistent with findings in the placenta of preeclampsia patients.Overexpression of LAM A3 significantly suppressed trophoblast cell invasion and migration abilities,while also up-regulating the phosphorylation levels of PI3K and Akt.Treatment with a PI3K inhibitor restored both cell function and phosphorylation lev-els to normal.Conclusion Elevated androgen levels in trophoblast cells from advanced maternal age induce specific changes in LAMA3 expression,and LAMA3 regulates trophoblast migration and invasion through the PI3K/Akt signaling pathway.
