Akademik Veri Yönetim Sistemi
ENDOCRINOLOGY, cilt.153, sa.5, ss.2486-2493, 2012 (SCI-Expanded)
Progesterone (P-4) signaling is critical for pregnancy. We previously showed that immunopilin FK506 binding protein (FKBP) 52 serves as a cochaperone to optimize progesterone receptor (PR) function in the uterus, and its deficiency leads to P-4 resistance in a pregnancy stage-specific and genetic background-dependent manner in mice. In particular, sc placement of SILASTIC implants carrying P-4 rescued implantation failure in CD1 Fkbp52(-/-) mice, but the resorption rate was substantially high at midgestation due to reduced P-4 responsiveness. Because downstream targets of P-4-FKBP52- PR signaling in the uterus to support pregnancy are not clearly understood, we performed proteomic analysis using Fkbp52(-/-), PR-deficient (Pgr(-/-)), and wild-type (WT) uteri. We found that the expression of galectin-1 (Gal1), an evolutionarily conserved glycan-binding protein, was significantly down-regulated in both Fkbp52(-/-) and Pgr(-/-) uteri compared with WT uteri. During early gestation, Lgals1, which encodes Gal1, was distinctly expressed in stromal and decidual cells. Lgals1 expression was much lower in d 4 Fkbp52(-/-) uteri compared with WT uteri, and this reduction was reversed by P-4 supplementation. More interestingly, concomitant supplementation of recombinant Gal1 significantly suppressed the high resorption rate and leukocyte infiltration at implantation sites in CD1 Fkbp52(-/-) females carrying P-4 SILASTIC implants. These findings suggest that uterine Gal1 is an important downstream target of P-4-FKBP52-PR signaling in the uterus to support P-4 responsiveness during pregnancy.