The Immunolocalization of Basic Fibroblast Growth Factor in the Mouse Uterus During the Initial Stages of Embryo Implantation

Abstract

Mammalian embryo implantation involves a series of complex interactions between maternal and embryonic cells. Uterine polypeptide growth factors may play critical roles in these cell interactions. Basic fibroblast growth factor (basic FGF) is a member of a family of growth factors. This growth factor may be potentially important for the process of embryo implantation because it (a) is stored within the extracellular matrix and is thus easily available during embryo invasion, (b) is a potent modulator of cell proliferation and differentiation and (c) stimulates angiogenesis. The immunolocalization of basic FGF in the uterus during the peri-implantation period of pregnancy is presented in this study. Uterine tissue samples were obtained on days 6-9 of pregnancy with day 1 of pregnancy being the day of a vaginal copulatory plug. Uterine samples were fixed in Bouin's fluid for no longer than 18 h. Following fixation and paraffin embedding, sections were exposed to primary antisera made in rabbits against either (a) human recombinant basic FGF or (b) 1-24 synthetic fragment of bovine basic FGF. The primary antibody was followed by biotinylated goat anti-rabbit IgG and a biotin-avidin-peroxidase complex. There were no differences in the immunolocalization of basic FGF using either source of primary antibody. Our results demonstrated both temporal and spatial changes in the localization of immunoreactive basic FGF within the implantation chamber during days 6-9 of pregnancy. Inter-implantation sites resembled the non-pregnant uterus with basic FGF present in extracellular matrices including basal laminae. On day 6 of pregnancy, decidual cells within the primary decidual zone lacked both intracellular and pericellular basic FGF while non-decidualized uterine stroma resembled inter-implantation sites. By days 7-8 of pregnancy, the secondary decidual zone had formed and was characterized by the distinct pericellular localization of basic FGF around individual decidual cells. By day 9 of pregnancy, the mesometrial region was forming and contained cords of decidual cells and a labyrinth of maternal blood vessels. The decidual cells contained diffuse intracellular basic FGF. Trophoblast cells were devoid of basic FGF at all times examined. These results indicate that basic FGF is present within the implantation chamber on days 6-9 of pregnancy and may be involved in the decidual cell response, trophoblast cell invasion and angiogenesis.

Heparanase Expression and Function During Early Pregnancy in Mice1

“…Thus, decidual HPSE is likely to cleave the HS components of the basal laminae as well as decidual HSPGs, facilitating embryo implantation by partially degrading or remodeling the extracellular matrix. In addition, HPSE is likely to release HSbinding growth factors involved in promoting embryo development or in the decidualization process [6,46,[55][56][57]. The activity assay indicated that the increase in HPSE activity greatly exceeded the increase in mRNA.…”

Angiogenesis in implantation

“…Interestingly, pseudo pregnancy selectively induces FGF2 mRNA in mesometrial tissue in rats and there is greater FGF2 immunolocalized in isolated mesometrial decidua cells than isolated anti-mesometrial cells [99]. FGF2 protein distribution also demonstrates temporal and spatial changes during the peri-implantation period in the rat [100].…”

FGFR-1 signaling is involved in spermiogenesis and sperm capacitation

“…A role for FGFR-1 signaling in suppressing premature capacitation is plausible as bFGF has been identified in the uterus of many species including humans, monkeys, pigs, mice and rats (Ferriani et al, 1993;Gupta et al, 1997;Reynolds et al, 1998;Rider et al, 1997;Samathanam et al, 1998;Sangha et al, 1997;Wordinger et al, 1994). We hypothesize that binding of bFGF (or an equivalent ligand) to FGFR-1 leads to activation of the PI3K pathway and the subsequent phosphorylation of an as yet to be identified 'master controller of capacitation' (MCC) (Fig.…”