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Insulin-Like Growth Factor Binding Proteins -1 and -3, and Hydroxysteroid (11-Beta) Dehydrogenase One: Potential Roles in Ruminant Conceptus Development and Endometrial FunctionSimmons, Rebecca M. 2009 December 1900 (has links)
Maternal contributions from the uterine endometrial luminal (LE) and glandular
(GE) epithelia are unequivocally required to support ruminant conceptus growth and
development, elongation and implantation. Therefore, studies were conducted to
examine expression of endometrial genes hypothesized to regulate conceptus
development.
The first study investigated two genes specifically expressed in the LE and
superficial GE of the ovine uterus. Insulin-like growth factor binding protein (IGFBP1)
and (IGFBP3) expression was coordinate with ovine conceptus elongation. Treatment
with P4 induced and IFNT stimulated IGFBP1, but not IGFBP3; however, IFNT only
moderately stimulated IGFBP1, indicating that another conceptus-derived factor
stimulates endometrial IGFBP1 expression. IGFBP1 did not affect proliferation of
ovine trophectoderm (oTr) cells in vitro, but stimulated their migration and attachment.
Results indicated that IGFBP1, but not IGFBP3 is a marker of conceptus elongation in
ruminants and stimulates cell migration and attachment.
The second study evaluated the effects of pregnancy, P4 and IFNT on expression
of hydroxysteroid (11-beta) dehydrogenases (HSD11B1 and HSD11B2), nuclear
receptor subfamily 3, group C, member 1 (NR3C1), and prostaglandin-endoperoxide
synthase 2 (PTGS2) in the ovine uterus. Expression of HSD11B1 mRNA and PTGS2
protein in endometrial LE and sGE were coordinate with conceptus elongation, while
HSD11B2 mRNA was expressed primarily in the conceptus. Further, P4 induced, but IFNT only moderately stimulated HSD11B1. Thus, HSD11B1 expression may be
regulated by prostaglandins (PGs) during early pregnancy. The presence of NR3C1 in
the ovine uterus implicates cortisol, the main product of HSD11B1, in peri-implantation
period events that include elongation of the ovine conceptus.
The third study determined in vivo effects of PGs on ovine conceptus elongation
and endometrial gene expression. Compared to control ewes, intrauterine infusions of a
PTGS2 inhibitor, meloxicam, retarded elongation and decreased expression of
elongation-related genes including IGFBP1, IGFBP3, HSD11B1, galectin 15
(LGALS15), solute carrier family 2, member 1 (SLC2A1), gastrin-releasing peptide
(GRP), cystatin C (CST3), radical S-adenosyl methionine domain containing 2 (RSAD2),
and ISG15 ubiquitin-like modifer (ISG15).
Collectively, these studies assessed the effects of pregnancy, P4, IFNT, and PGs
on endometrial genes implicated in conceptus growth. These results indicate that
IGFBP1 is a marker of conceptus elongation in ruminants and provide novel roles for
both cortisol and PGs in endometrial gene expression and conceptus elongation.
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