Decidual senescence in recurrent pregnancy loss: forkhead box M1-targeted progesterone treatment

Abstract

Research question What is the role of FOXM1 in the pathogenesis of recurrent pregnancy loss (RPL) characterized by increased decidual senescence, and how do two progesterone analogues (medroxyprogesterone acetate [MPA] and dydrogesterone [DYD]) modulate FOXM1 expression and associated senescence markers in an in-vitro decidualization model? Design Primary decidual cells were isolated from decidual tissue samples collected from women with clinically healthy pregnancies that were terminated voluntarily (control pregnancy group, n = 10) and women with RPL (RPL group, n = 10). Cells were treated with MPA and DYD, and PRL and IGFBP-1 concentrations were analysed by ELISA. FOXO1, FOXM1, phospho-FOXM1 (p-FOXM1), DIO2 and β-GAL expression was examined by immunofluorescence. Co-culture experiments with AC-1M88 trophoblast-like cells assessed spheroid expansion and migration. Results MPA and DYD treatments significantly ameliorated PRL (P = 0.006 and P = 0.015, respectively) and IGFBP-1 (both P