Galectin-1 Markedly Reduces the Incidence of Resorptions in Mice Missing Immunophilin FKBP52

Abstract

Progesterone (P4) 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 P4 resistance in a pregnancy stage-specific and genetic background-dependent manner in mice. In particular, sc placement of SILASTIC implants carrying P4 rescued implantation failure in CD1 Fkbp52 / mice, but the resorption rate was substantially high at midgestation due to reduced P4 responsiveness. Because downstream targets of P4- 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 P4 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 P4 SILASTIC implants. These findings suggest that uterine Gal1 is an important downstream target of P4-FKBP52-PR signaling in the uterus to support P4 responsiveness during pregnancy.