In vitro fertilization-associated osteomodulin upregulation is linked to impaired placental angiogenesis.

INTRODUCTION

Assisted reproductive technology (ART) is associated with increased risks of adverse perinatal outcomes, potentially linked to placental dysfunction. Previous transcriptomic profiling identified osteomodulin (OMD) upregulation in IVF placentas, but its role in placental vascular regulation remains unclear. This study investigated OMD expression in IVF placentas and its potential effects on endothelial angiogenic function.

METHODS

Term placental tissues were collected from uncomplicated singleton IVF and spontaneously conceived pregnancies (n = 6/group), with a subset used for molecular analyses (n = 3/group). Third-trimester maternal serum samples were also obtained (n = 19/group). OMD expression was assessed by ELISA, qRT-PCR, Western blotting, and immunohistochemistry. Human umbilical vein endothelial cells (HUVECs) were used to establish OMD overexpression and siRNA-mediated knockdown models. Endothelial proliferation, migration, invasion, and tube formation were evaluated. RNA sequencing, GO/KEGG enrichment, and target validation were performed.

RESULTS

OMD levels were increased in maternal serum and placental tissues from the IVF group compared with the spontaneously conceived group. Immunostaining suggested stronger OMD staining in syncytiotrophoblasts and placental vascular regions. OMD overexpression suppressed HUVEC proliferation, migration, invasion, and tube formation, whereas OMD knockdown enhanced proliferation, invasion, and tube formation. Transcriptomic analysis implicated cell-matrix interaction, focal adhesion, and PI3K-AKT signaling pathways. THBS1 expression increased with OMD overexpression and decreased after OMD knockdown, and placental THBS1 staining was higher in the IVF group.

DISCUSSION: Elevated OMD expression in IVF placentas was associated with altered endothelial cell behavior in vitro, potentially involving THBS1 and PI3K-AKT-related signaling. These findings may provide mechanistic insight into placental vascular alterations associated with IVF pregnancies.