Paracrine effects of bFGF and KGF on the process of mouse blastocyst implantation

Abstract

Implantation is a complex process that requires the interaction of the blastocyst, and subsequently, that of the developing embryos with the endometrium. Several growth factors and cytokines are involved in implantation, but the details of their actions as related to the regulation of blastocyst implantation remain unclear. In the present study, the RT‐PCR method was used to determine the gene expression of basic fibroblast growth factor (bFGF), keratinocyte growth factor (KGF), FGF receptor 1 (FGFR1), FGF receptor 2 (FGFR2), and KGF receptor (KGFR) in mouse embryos and in the stromal and epithelial cells of the uterine endometrium. Basic FGF and KGF mRNA were expressed in the endometrial cells, but were not expressed in the embryos. The mRNAs of receptors for bFGF and KGF were expressed in the blastocysts and in the in vitro implanting embryos, suggesting that bFGF and KGF may exert paracrine effects on blastocyst implantation. In this mouse model of blastocyst implantation, it was found that transforming growth factor α (TGF‐α) at the concentrations of 1 ng/ml and 10 ng/ml significantly enhanced the blastocyst attachment and trophoblast spreading and increased trophoblast surface area. Relatively high concentrations of bFGF (100–500 ng/ml) significantly enhanced the rates of blastocyst attachment and of trophoblast spreading and promoted the expansion of the surface area of the implanting embryos. Unlike the rates of blastocyst attachment and trophoblast spreading, the surface area of the spreading embryos was significantly increased by addition of KGF (1–100 ng/ml). These results suggest that the bFGF and KGF derived from the endometrial cells exert paracrine effects on the process of implantation by stimulating trophoblast outgrowth through their cognate receptors. Mol. Reprod. Dev. 50:54–62, 1998. © 1998 Wiley‐Liss, Inc.

A FGF2-mediated incoherent feedforward loop induces Erk inhibition and promotes naïve pluripotency

“…This suggests that FGF2 may be part of the embryo niche (Figure 7). This is supported by several reports (Wordinger et al, 1992;Carlone and Rider, 1993;Taniguchi et al, 1998;Paria et al, 2001;Yang et al, 2015). Interestingly, this is reminiscent of the maternal expression of LIF, a key regulator of both naïve pluripotency and implantation (Stewart et al, 1992;Ying et al, 2008), highlighting that the early embryo may integrate different signals from the its niche.…”

“…Maternal expression of LIF, another crucial factor for naïve pluripotency is in fact well documented {Stewart, 1992 #190} and FGF2 has also been postulated to be expressed both in trophoblast cells and in maternal (endometrial) tissues (Wordinger et al ., 1992; Carlone and Rider, 1993; Taniguchi et al ., 1998; Paria et al ., 2001; Yang et al ., 2015).…”

Supplementation with fibroblast growth factor 7 during in vitro maturation of porcine cumulus-oocyte complexes improves oocyte maturation and early embryonic development

“…Subsequent investigations could direct their focus toward elucidating the role of FGF7 in the IVF outcomes, possibly FGF7 play primary role in IVF-grown blastocysts. Additionally, with regard to late blastocyst development, research in mice demonstrated that FGF7 treatment can promote blastocyst implantation (77). In pigs and humans, FGF7 can regulate the interaction between the developing embryo with the endometrium (63,78).…”

The transcriptional repressor Blimp1/PRDM1 regulates the maternal decidual response in mice

“…Upregulated Fgf expression could potentially lead to ectopic activation of the P-TGC subset. Addition of Fgf7 to cultured blastocysts results in increased P-TGC numbers and precocious differentiation 51 . Blimp1 probably dampens Fgf7 signalling to maintain the balance of TGC proliferation versus differentiation within the decidual stroma.…”