The actions of fibroblast growth factors during periimplantation conceptus development in cattle

• Main Author: Yang, Qien
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2010
• Subjects: Animal sciences; Cellular biology; Developmental biology
• ISBN: 1124516549; 9781124516547

In ruminants, the trophoblast product interferon tau (IFNT) acts as an anti-luteolytic hormone to maintain a pregnant state and promote uterine receptivity for subsequent embryo development and implantation. Defects in early embryo development and miscues between the embryo and uterus result in pregnancy failure in various species. Lactating dairy cattle are especially prone to early pregnancy losses and these pregnancy loss lead to low reproductive efficiency and substantial economic losses. The fibroblast growth factor (FGF) family plays critical roles in regulating early embryonic development in mammals. In cattle and sheep, it is clear that several uterine-derived FGFs stimulate IFNT production in trophoblast cells. One of particular interest is FGF2. It is synthesized by epithelial cells and released into the uterine lumen in cyclic and pregnant animals. In the presence of a conceptus, FGF2 binds to its receptors on trophoblast cells and increases IFNT mRNA transcription and bioactive protein synthesis and release. Herein, three projects were completed to examine the signaling component that mediates FGF-induced IFNT production in bovine trophoblast cells and to discover additional biological roles of uterine- and conceptus-derived FGFs during bovine embryogenesis. The first set of studies investigated the signaling pathways triggered by FGF2 to stimulate IFNT production. Using two bovine trophoblast cell lines and primary trophoblast outgrowths as model systems, the work revealed that ERK1/2 and p38MAPK are critical for basal expression of IFNT , while protein kinase C (PKC) delta mediates FGF2-induced IFNT expression. Another set of studies revealed a new activity for FGF2 during bovine embryo development. Specifically, FGF2 promoted primitive endoderm formation in bovine blastocysts. Activation of FGF signaling or inhibition of FGFR kinase activity in blastocysts modulated early lineage marker expression. A final set of experiments was completed to test the hypothesis that FGF2 or FGF10, a conceptus derived FGF, regulated trophoblast cell migration. FGF2 and FGF10 activated multiple MAPK pathways and the ERK1/2, p38 MAPK and SAPK/JNK signaling modules regulated FGF-mediated systems to stimulate trophoblast migration in vitro. Also, treatment of blastocysts or trophoblast cells with FGF2 modulated the expression of migration-related genes ( ITGA2B, ITGB6 and MMP2). Taken together, current data suggest that FGF-dependent signals play crucial roles in conceptus growth and differentiation during pre- and peri-implantation development. Understanding the fundamental biology of embryo development at this stage will provide the basis to develop strategies to reduce early pregnancy loss. (Full text of this dissertation may be available via the University of Florida Libraries web site. Please check http://www.uflib.ufl.edu/etd.html)