Regulation of Expression of Fibroblast Growth Factor 7 in the Pig Uterus by Progesterone and Estradiol1

Abstract

Fibroblast growth factor 7 (FGF7) stimulates cell proliferation, differentiation, migration and angiogenesis. The consensus is that FGF7, expressed by mesenchymal cells, binds FGF receptor 2IIIb (FGFR2) on epithelia, thereby mediating epithelial-mesenchymal interactions. The pig uterus is unique in that FGF7 is expressed by the luminal epithelium (LE) and FGFR2 is expressed by the LE, glandular epithelium (GE), and trophectoderm to effect proliferation and differentiated cell functions during conceptus development and implantation. FGF7 expression by the uterine LE of pigs increases between Days 9 and 12 of the estrus cycle and pregnancy, as circulating concentrations of progesterone increase, progesterone receptors (PGR) in the uterine epithelia decrease, and the conceptuses secrete estradiol-17beta (E(2)), for pregnancy recognition. Furthermore, E(2) increases the expression of FGF7 in pig uterine explants. The present study investigates the relationships between progesterone, E(2), and their receptors and the expression of FGF7 in the pig uterus in vivo. Pigs were ovariectomized on Day 4 of the estrus cycle and injected i.m. daily from Day 4 to Day 12 with either corn oil (CO), progesterone (P4), P4 and ZK317,316 (PZK), E(2), P4 and E(2) (PE), or P4 and ZK and E(2) (PZKE). All gilts (n = 5/treatment) were hysterectomized on Day 12. The results suggest that: 1) P4 is permissive to FGF7 expression by down-regulating PGR in LE; 2) P4 stimulates PGR-positive uterine stromal cells to release an unidentified progestamedin that induces FGF7 expression by LE; 3) E(2) and P4 can induce FGF7 when PGR are rendered nonfunctional by ZK; and 4) E(2) from conceptuses interacts via estrogen receptor alpha, but not estrogen receptor beta in LE to induce maximal expression of FGF7 in LE on Day 12 of pregnancy in pigs.

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

“…In gilts, FGF7 has specific expression in the LE during conceptus elongation, which is coincident with the downregulation of PGR. In addition, its expression is dependent on an interplay between P 4 , E 2 and oestrogen receptor a (Ka et al 2007). However, results from this study as well as data in the literature indicate that FGF7 is unlikely to play a significant role in early pregnancy in ruminants.…”

Comparative aspects of implantation

“…High levels of IFNG may act on uterine stroma and GE to increase intracellular interferon-stimulated gene factor 3 (ISGF3) that permits lower levels of IFND to maximally upregulate STAT1 expression in close proximity to the implanting pig conceptus. To date, a limited number of estrogen-and IFN-stimulated genes have been localized in pig endometrium (see Hicks et al 2003, White et al 2005, Joyce et al 2007a, 2007b, Ka et al 2007, Ross et al 2007, So et al 2008, Song et al 2009). Type I and type II IFNs each induce expression of largely nonoverlapping sets of genes and they may also have synergistic interactions to affect physiological responses (see Levy et al 1990).…”

“…Pig blastocysts are not invasive in the uterus likely because of abundant secretion of protease inhibitors by uterine epithelia (Fazleabas et al 1982), but pig blastocysts are invasive when transferred to an ectopic site such as kidney capsule (Samuel & Perry 1972). Therefore, contrary to dogma, uterine LE is in direct contact with non-invasive conceptus trophectoderm cells that express FGFR2(IIIb) respond directly to FGF7 with respect to proliferation and differentiated functions of trophectoderm cells in pigs (see Ka et al 2007. In ruminants, uterine LE and conceptus trophectoderm interact to form BNC that produce PRL3D1 and form…”

Novel insights into the mechanisms of pregnancy establishment: regulation of prostaglandin synthesis and signaling in the pig

“…However, PGR are maintained in stroma and myometrium. Therefore, the effects of ovarian progesterone on expression of many factors in LE may be mediated indirectly either by progesterone-induced progestamedins produced by PGR-positive stromal cells or by induction of molecules in LE that causes downregulation of PGR to regulate expression of endometrial genes , Ka et al 2007). Downregulation of PGR in LE and GE coincides with activation of nuclear factor kappa B (NFKB); however, a role of this transcription factor in inhibition of PGR expression was not confirmed in the pig (Ross et al 2010, Mathew et al 2011.…”