Decidual cell invasion and decidualization at the trophoblast-decidual interaction in the progression of cesarean scar pregnancy

KISS1 plays a role in the trophoblast in terms of imbalances in trophoblast-decidua interactions during cesarean scar pregnancy (CSP). However, genes in decidual cells remain poorly understood. To elucidate the role of the KISS1 gene in the invasion process of decidual cells during the progression of CSP, decidual tissue samples were collected from the basal decidua from CSP implantation sites and normal first-trimester intrauterine pregnancies (IUPs). Single-cell RNA sequencing was performed to assess cellular heterogeneity and investigate the functional characteristics of cells at the trophoblast-decidua interface. Immunohistochemistry, qRTPCR and Western blotting were used to detect KISS1 expression in CSP and IUP decidual cells. RNA interference and overexpression experiments were conducted to further validate the function of the KISS1 gene in migration and invasion. The mechanism by which KISS1 activates molecules was validated through RNA-seq combined with luciferase assays. Among all cell types, the decidual stromal cell population exhibited decreased KISS1 expression, which was accompanied by the downregulation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. KISS1 expression levels in decidual cells were significantly lower in the CSP group than in the IUP group (P < 0.001). siKISS1 reduced the invasion and migration of decidual cells, whereas overexpression of KISS1 reversed these effects. siKISS1 decreased p-AKT expression in decidual cells, whereas overexpression of KISS1 significantly increased p-AKT expression levels. KISS1 was significantly upregulated by miR-6809 but downregulated by miR-4768. Our results indicate that the downregulation of KISS1 expression may play a crucial role in the decidualization process of CSP by influencing trophoblast-decidua interactions.