Fibroblast Growth Factor-10: A Stromal Mediator of Epithelial Functionin the Ovine Uterus

Abstract

Fibroblast growth factor-10 (FGF-10) is a stromal-derived paracrine growth factor considered to be important during embryogenesis; however, its expression by cells in the female reproductive tract has not been investigated. Therefore, an ovine FGF-10 cDNA was cloned from an ovine endometrial cDNA library to investigate expression and potential paracrine characteristics of FGF-10 in the ovine uterus. The ovine FGF-10 cDNA encodes a protein of 213 amino acids and possesses an unusually long 5' untranslated region (UTR). In situ hybridization demonstrated that ovine FGF-10 mRNA was expressed by endometrial stromal cells and by mesenchymal cells of the chorioallantoic placenta. The mRNA for FGF-7, a homologue of FGF-10, was localized in the tunica muscularis of blood vessels in endometrium and myometrium. In contrast, FGF receptor 2IIIb, the high-affinity receptor for both FGF-10 and FGF-7, was expressed exclusively in luminal epithelium, glandular epithelium, and placental trophectoderm. The in vivo spatial expression pattern suggests that FGF-10 is a novel endometrial stromal cell-derived mediator of uterine epithelial and conceptus trophectodermal functions. The nonoverlapping spatial patterns of expression for FGF-10 and FGF-7 in ovine uterus and conceptus suggest independent roles in uterine function and conceptus development.

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

“…Also, at least two of the primary receptor partners for FGF2, R1c, and R3c, preside in ovine conceptuses (Ornitz 2000, Powers et al 2000, Ocon-Grove et al 2008). An additional receptor subtype, R2b, is also produced by ovine conceptuses (Chen et al 2000, Ocon-Grove et al 2008. FGF2 interacts with R2b with a lower affinity than R1c and R3c (Ornitz 2000, Powers et al 2000), thereby suggesting that additional FGFs may impact conceptus development by acting through R2b.…”

“…FGF7 was not amplified in day 17 conceptus and CT1 samples but was detected in control samples (endometrium and lung). Bovine endometrium was included as a positive control based on previous work describing endometrial FGF1, 2, 7, and 10 expression in cyclic and pregnant cows and ewes (Chen et al 2000, Pfarrer et al 2006, Michael et al 2006, Ocon-Grove et al 2008. DNA sequencing verified that each PCR product represented the FGFs of interest (data not shown).…”

“…The relative amount of FGF10 mRNA rivaled that of FGF2 in day 14 conceptuses and represented to predominant FGF transcript in day 17 conceptuses. Chen et al (2000) identified that the extraembryonic mesoderm is the primary site of FGF10 expression in ovine conceptuses. The extraembryonic mesoderm emerges from the epiblast (i.e., the gastrulating inner cell mass) around days 14-16 of pregnancy in cattle and soon thereafter extends between the trophectoderm and endoderm to establish the inner chorionic layer and the outer yolk sac layer (Betteridge & Flechon 1988, Hue et al 2001, Maddox-Hyttel et al 2003, Degrelle et al 2005, Robinson et al 2006.…”

“…This certainly is the case for the R2b subtype. Its transcripts localize to ovine and bovine trophectoderm during peri-and postattachment development (Chen et al 2000, Pfarrer et al 2006. R2b is also expressed by the uterine epithelium in ewes where it appears to play a central role in regulating uterine activity during pregnancy by interacting with stromal-derived FGF10 (Chen et al 2000).…”

“…Transcripts for FGF2 and several FGFR spliced variants are detected in elongated ovine conceptuses (Ocon-Grove et al 2008). Also, transcripts for FGF1, 2, 7, and 10 and several FGFRs exist in post-attachment stage placentae in sheep and cattle (Chen et al 2000, Pfarrer et al 2006. These FGFs likely facilitate placental development in a variety of ways throughout gestation.…”