Temporal regulation of fibroblast growth factors and their receptors in the endometrium and conceptus during the pre-implantation period of pregnancy in cattle

Abstract

We hypothesised that the expression pattern of members of the fibroblast growth factor (FGF) family would be altered in the endometrium as the oestrous cycle/early pregnancy progressed associated with changes in the expression pattern of their receptors in the developing embryo/conceptus. Expression of FGF1 and FGF10 transcript variants 1 and 2 increased significantly as the oestrous cycle/early pregnancy progressed. Neither progesterone (P 4 ) supplementation nor pregnancy status significantly affected the expression of any of the FGF ligands studied. However, there was a significant interaction between day, pregnancy and P 4 status on FGF2 expression (P!0.05) and a significant interaction between P 4 status and day on FGF10_tv2 expression. FGF10 protein was localised in the luminal and glandular epithelium as well as the stroma but was not detected in the myometrium. By RNA sequencing, the expression of FGF ligands in the developing embryo/conceptus was found to be minimal. The expression of FGF receptor 1 (FGFR1), FGFR2, FGFR3, FGFR4, FGFRL1 and FRS3 was significantly affected by the stage of conceptus development. Interestingly, the expression of FGFR1 and FGFR4 was higher during early embryo development (days 7-13, P!0.05) but decreased on day 16 (P!0.05) while FGFR2 (P!0.001) expression was similar from day 7 through to day 13, with a significant increase by day 16 (P!0.05) that was maintained until day 19 (PO0.05). In conclusion, these data demonstrate that FGF ligands are primarily expressed by the endometrium and their modulation throughout the luteal phase of the oestrous cycle/early pregnancy are associated with alterations in the expression of their receptors in the embryo/conceptus.

Fibroblast growth factor 2 induces proliferation and distribution of G2/M phase of bovine endometrial cells involving activation of PI3K/AKT and MAPK cell signaling and prevention of effects of ER stress

“…Progesterone‐induced FGF10 regulates ovine endometrial functions during early gestational by maintaining a uterine environment conducive to pregnancy (Satterfield et al, ). In addition, FGF10 is expressed by bovine conceptuses during elongation in a pattern similar to that for IFNT and it is also expressed in bovine endometrium and ovarian follicles (Buratini et al, ; Okumu et al, ). FGF2 is also essential for successful development of conceptus and uteri in various species.…”

Initiation of Conceptus Elongation Coincides with an Endometrium Basic Fibroblast Growth Factor (FGF2) Protein Increase in Heifers

“…The bovine endometrium expresses FGF1 and FGF2, and the modulation of these two FGF isoforms from Days 5 to 16 in both cyclic and pregnant heifers have been reported [11]. In pregnant heifers, the gene expression of FGF1 and FGF2 in the endometrium relate to changes in the expression of their receptors in the conceptus [11].…”

“…The bovine endometrium expresses FGF1 and FGF2, and the modulation of these two FGF isoforms from Days 5 to 16 in both cyclic and pregnant heifers have been reported [11]. In pregnant heifers, the gene expression of FGF1 and FGF2 in the endometrium relate to changes in the expression of their receptors in the conceptus [11]. The bovine uterine epithelium and the conceptus synthesize FGF2, and, between Days 14 and 17, FGF gene expression increases in the elongating conceptuses [12].…”

“…This indicates that FGF1 and FGF2 play critical roles during preimplantation in cattle. The pregnancy status itself as well as the concentrations of progesterone (P4) appear not to substantially affect the endometrial tissue gene expression of the ligands (FGF1 and FGF2) in cattle, while the expression of the respective receptors strongly depends on the conceptus developmental stage [11]. However, the involvement of FGF during the period of initiation of the implantation process at around Day 18 in cattle is not known.…”

“…However, the involvement of FGF during the period of initiation of the implantation process at around Day 18 in cattle is not known. In cattle, the period from Days 7 to 19 of pregnancy is critical as it comprises the period of conceptus elongation, pregnancy recognition, and the initiation of the implantation process [11]. We aimed at elucidating the modulation of endometrial and embryonic acidic and basic FGF and the associated receptors during the preimplantation phase in cattle.…”