Spatial and Temporal Analyses of FGF9 Expression During Early Pregnancy

Abstract

Background: Fibroblast growth factors (FGFs), in complex with their receptors (FGFRs), regulate a broad spectrum of biological functions including cellular proliferation, survival, migration, and differentiation. In human endometrial stromal cells, FGF9 is regulated with estrogen (E). Methods/Results: First, we report that in uterus tissue of ovariectomized wild type mice, FGF9 is present in three isoforms and is regulated with E. Second, we found that during peri-implantation, Fgf9 expression reached its peak at day 4.5 of pregnancy. Immunofluorescence analyses demonstrated overlapping FGF9 and COX2 expression surrounding the blastocyst attachment site. Next, we identified FGF9- and CD31-positive cells as a part of the microvessels; however, expression was localized to a distinct population of cells. Finally, our data showed synchronized, spatial expression of FGF9 on the luminal epithelium with FGFR2 present on the trophectoderm. Conclusion: Our data suggest that FGF9 is a crucial factor required to establish the appropriate microenvironment for successful implantation and the maintenance of pregnancy.

High Mobility Group Box 1 Regulates Uterine Decidualization through Bone Morphogenetic Protein 2 and Plays a Role in Kruppel-Like Factor 5-Induced Stromal Differentiation

“…In this study, we showed that Hmgb1 mRNA was obviously observed in uterine epithelium on day 2 and 3 of pregnancy when uterus was pre-receptive, but its expression was scarcely detected with the attainment of uterine receptivity on day 4, which was consistent with that in human and rat uteri [14,22,23], suggesting a potential role of Hmgb1 in preparation for uterine receptivity which was required for successful embryo implantation. With implantation in progress on day 5, the accumulation of Hmgb1 mRNA was distinctly noted in the subluminal stroma surrounding the blastocyst at implantation sites, reinforcing the importance of Hmgb1 in embryo implantation.…”

Maternal Recognition of Pregnancy in the Horse: Are MicroRNAs the Secret Messengers?

“…Common upregulation in the endometrium of pregnant mares was found for several genes involved in key pathways at the embryo-maternal interface. This included upregulation of secretory molecules, namely insulin like growth factor binding protein 1 (IGFBP1), fibroblast growth factor 9 (FGF9), and TIMP metallopeptidase inhibitor 1 (TIMP1), which support embryonic development as well as endometrial proliferation and endometrial tissue remodeling during implantation [37][38][39]; IGFBP1 and TIMP1 have also been shown to inhibit trophoblast invasiveness. Common heat shock proteins were heat shock protein family B (small) member 8 (HSPB8) and crystallin alpha B (CRYAB), which are regulated by estrogens and involved in endometrial receptivity and implantation in human [40,41].…”

“…Upregulation of FGF9 during pregnancy was highly significant. Its expression is induced by PGE2 and by estrogen and a recent study associated local PTGS2 enzymatic activity with FGF9 expression at the site of embryo implantation, highlighting a crucial role of FGF9 for the establishment and maintenance of pregnancy in mice [38,47]. The equine conceptus produces both estrogens and PGE2 [17], but their role as signaling factor for MRP has not been evidenced.…”

The genetic architecture of sporadic and multiple consecutive miscarriage

“…4a). FGF9 is needed for creating a favorable microenvironment for embryo implantation/pregnancy maintenance, possibly either by regulating angiogenesis or participating in recognizing competent blastocysts via the maternal FGF9/embryonic FGFR2 axis 43 . If this 'embryo sensoring' is compromised, implantation of lowquality embryos can occur and potentially result in miscarriage 44 .…”