Several fibroblast growth factors are expressed during pre-attachment bovine conceptus development and regulate interferon-tau expression from trophectoderm

Abstract

The trophectoderm-derived factor interferon tau (IFNT) maintains the uterus in a pregnancy-receptive state in cattle and sheep. Fibroblast growth factors (FGFs) are implicated in regulating IFNT expression and potentially other critical events associated with early conceptus development in cattle. The overall objectives of this work were to identify the various FGFs and FGF receptors (FGFRs) expressed in elongating pre-attachment bovine conceptuses and determine if these FGFs regulate conceptus development and/or mediate IFNT production. In vitro-derived bovine blastocysts and in vivo-derived elongated conceptuses collected at day 17 of pregnancy express at least four FGFR subtypes (R1c, R2b, R3c, R4). In addition, transcripts for FGF1, 2, and 10 but not FGF7 are present in elongated bovine conceptuses. The expression pattern of FGF10 most closely resembled that of IFNT, with both transcripts remaining low in day 8 and day 11 conceptuses and increasing substantially in day 14 and day 17 conceptuses. Supplementation with recombinant FGF1, 2 or 10 increased IFNT mRNA levels in bovine trophectoderm cells and bovine blastocysts and increased IFNT protein concentrations in trophectoderm-conditioned medium. Blastocyst development was not affected by any of the FGFs. In summary, at least four FGFRs reside in pre-and peri-attachment bovine conceptuses. Moreover, conceptuses express at least three candidate FGFs during elongation, the time of peak IFNT expression. These findings provide new insight for how conceptus-derived factors such as FGF1, 2, and 10 may control IFNT expression during early pregnancy in cattle.

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

“…In the bovine endometrium, FGF1 levels in the current study were similar on days 5 and 7 and then decreased through to day 16. This is in contrast to expression in the bovine conceptus where levels were low on days 11 and 14 and increased on day 17 (Cooke et al 2009). We therefore propose that endometrial-derived FGF1 may be required as the embryo develops to the blastocyst stage but subsequently other FGF family members, such as FGF10, play a role in conceptus development in cattle.…”

“…Only FGF2 could be detected in culture, while FGF10 was undetectable in in vitro-produced embryos. On the other hand, in in vivo produced embryos, FGF1 and FGF10 were detectable in addition to FGF2 (Cooke et al 2009). This indicates a possible crucial role of the endometrium and/or its secretions in the subsequent expression of the FGFs by the embryo; for example, in sheep, FGF10 is expressed in the endometrium but its receptors are found in the foetal trophectoderm cells, where they mediate mesenchymal-epithelial interactions (Chen et al 2000).…”

“…FGF10 mRNAs have also been detected in ovine endometrial tissue where it has been implicated in endometrial function as well as in growth and development of the conceptus (Satterfield et al 2008). In cattle, FGF10 is expressed by the conceptus (Cooke et al 2009) and other reproductive tissues such as follicles, where it is involved in mediating signals from theca cells and/or oocytes to granulosa cells (Buratini et al 2007); furthermore, its addition to culture medium enhances bovine oocyte maturation and developmental competence (Zhang et al 2010).…”

Effect of Fibroblast Growth Factor 2 (FGF2) and Insulin Transferrin Selenium (ITS) on In Vitro Maturation, Fertilization and Embryo Development in Sheep

“…FGF2 as an oocyte competency factor was investigated because it has been produced by theca, granulosa and cumulus cells throughout folliculogenesis (Berisha et al 2006). The transcripts for receptors for FGF2 and many other FGFs were evident in bovine and ovine blastocysts and peri-implantation bovine and ovine conceptuses (Cooke et al 2009). Since FGF2 is reported to be endogenously produced by cumulous cells (Berisha et al 2006), it was hypothesized that additional supplementation of FGF2 might improve oocyte development (Gupta et al 2002).…”

Fibroblast growth factors activate mitogen-activated protein kinase pathways to promote migration in ovine trophoblast cells

“…Both FGFs are produced in early pregnancy. FGF2 is produced primarily in luminal and glandular epithelium throughout the estrous cycle and early pregnancy in cattle and sheep (Ocó n-Grove et al 2008, Cooke et al 2009). In the ewe, uterine luminal FGF2 protein concentrations increase at days 12-13 post-estrus coincident with conceptus elongation in this species (Ocó n- Grove et al 2008).…”