PubMed Health⌕ Search

Biomedical subjects

S Srisuparp

Publications and source records attributed to S Srisuparp.

4 recordsLinked to original sources

Uterine receptivity in the baboon: modulation by chorionic gonadotropin.

Embryonic signals not only rescue the corpus luteum but also modulate the uterine environment in preparation for implantation. Chorionic gonadotropin (CG), an early embryonic signal, is one such molecule. In vivo studies in the baboon show that CG alters the morphology and biochemical activity of the uterus, especially with respect to the three major cell types: luminal epithelium, glandular epithelium, and stromal fibroblasts. Further, CG and progesterone have a synergistic effect on the receptive endometrium. CG action on the endometrial cells is transduced via a seven transmembrane G protein-coupled receptor. Possible signaling pathways involved are discussed.

Animals↗

Interleukin-1beta induces the expression of insulin-like growth factor binding protein-1 during decidualization in the primate.

Since interleukin (IL)-1 can modulate fetal/maternal interactions, we hypothesized that IL-1beta is one potential embryonic cytokine that regulates the conceptus-induced decidual response in baboon stromal fibroblasts. Treatment of stromal fibroblasts with IL-1beta (10 ng/ml, 10 min) resulted in the phosphorylation of p38 mitogen-activated protein kinase and IkappaB-alpha. This suggests that IL-1beta induces multiple signaling pathways in stromal cells that result in the activation of mitogen-activated protein kinase cascade and the transcription factor NF-kappaB. After 4 h of stimulation, IL-1beta induced gene expression of cyclooxygenase-2 (COX-2) but not cyclooxygenase-1 (COX-1). PGE2 synthesis paralleled COX-2 messenger RNA expression. The addition of hormones [36 nM estradiol-17beta, 1 microM medroxyprogesterone acetate, and 100 ng/ml relaxin] to IL-1beta-treated cells induced insulin-like growth factor binding protein-1 (IGFBP-1) messenger RNA expression after 3 days of incubation. A specific COX-2 inhibitor, NS 398 (10 nM), partially inhibited IGFBP-1 protein synthesis. In contrast, the induction of IGFBP-1 by N6, 2'-O-dibutyryladenosine 3:5'-cyclic monophosphate (dbcAMP) and hormones was not affected by NS 398 treatment. Both dbcAMP and IL-1beta, in the presence of hormones, can independently induce IGFBP-1 gene expression and decidualization. However, if IL-1beta and dbcAMP were added together, IGFBP-1 expression was inhibited. These data suggest that IL-1beta can activate multiple signaling pathways that either positively or negatively regulate IGFBP-1 gene expression and decidualization.

Animals↗

IL-1beta during in vitro decidualization in primate.

The sequence of biochemical and molecular events associated with decidualization in the primate remain unclear. In the baboon, the sequential changes during this period in vivo are characterized by the downregulation of alpha-smooth actin followed by induction of cyclooxygenase-2 (COX-2) at the implantation site and the expression of insulin growth factor binding protein-1 (IGFBP-1). IGFBP-1 is the predominant protein in decidualized cells and is considered to be biochemical marker of decidualization. In the baboon the expression of IGFBP-1 requires the presence of a conceptus in vivo or N(6), 2'-O-dibutyryladenosine 3:5'-cyclic monophosphate (dbcAMP) in the presence of hormones in vitro. In addition IL-1beta, as a possible conceptus-mediated factor, can induce IGFBP-1 expression in the presence of hormones following 3 days of incubation. However, if IL-1beta and dbcAMP are added together, IGFBP-1 expression is inhibited which resulted in IL-1beta being considered to be "inhibitory" to decidualization. Current data suggest that IL-1beta can activate multiple signaling pathways that either positively (no exogenous cAMP) or negatively (in presence of exogenous cAMP) regulate IGFBP-1 gene expression and decidualization in vitro. Signaling pathways activated by IL-1beta following 10 min of stimulation result in the phosphorylation of mitogen-activated protein kinase (MAPK, specifically p38 MAPK) and also lead to NF-kappaB activation. The expression of COX-2 and matrix metalloproteinase-3 (MMP-3) genes follows after 4-6 h. The steroid hormones, particularly progesterone, which are critical for IGFBP-1 expression, modulate the activity of IL-1beta by down-regulating MMP-3 activity. Disruption of actin filaments enhances IGFBP-1 induction during decidualization. IL-1beta induced MMP-3 may upregulate IGFBP-1 by initiation of cytoskeletal reorganization through degradation of extracellular matrix (ECM). Inhibition of IL-1beta induced pathways leads to reduction of IGFBP-1 expression, suggesting that IL-1beta may be involved in the events leading to decidualization in baboons.

Animals↗

The role of chorionic gonadotropin (CG) in blastocyst implantation.

Implantation is a complex spatio-temporal interaction between the genotypically different embryo and the mother. Success of this event requires the synchronization of development and effective biochemical communications from both sides. Chorionic gonadotropin (CG), which is a major embryonic signal in the primate, is a glycoprotein hormone synthesized and secreted by the trophoblast. Various isoforms exist in plasma, urine, and blastocyst culture medium, a result of posttranslational modifications. The exponential secretion of CG and its long circulatory half-life extends the life span of corpus luteum to maintain the supply of progesterone during the first 6-8 weeks of pregnancy. To study the direct effects of CG in the uterus, we used the baboon (Papio anubis) as a non-human primate model. In vivo stimulation with CG during the window of uterine receptivity results in further morphologic and biochemical modifications of the receptive endometrium. These are characterized by the plaque reaction in the luminal epithelium, an increase in glycodelin expression and secretion by the glandular epithelium, and the differentiation of subepithelial stromal fibroblasts characterized by expression of the alpha smooth muscle actin (alpha SMA). Pretreatment with progesterone receptor antagonist (PRa) completely or partially inhibits these effects. The signal transduction pathway activated by CG in primate endometrial epithelial cells involves the protein kinase A (PKA)-independent phosphorylation of extracellular signal regulated kinase (ERK 1/2). This alternate signal transduction pathway may prevent CG Receptor (R) downregulation at the implantation site and enhance epithelial cell proliferation and differentiation. Thus, our results suggest that CG plays an important role in implantation in addition to its luteotrophic role.

Alternative Splicing↗