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

Reproduction ◽  
2011 ◽  
Vol 142 (3) ◽  
pp. 389-399 ◽  
Author(s):  
Agnieszka Waclawik

Ovarian progesterone induces essential changes leading to a temporary state of uterine receptivity for conceptus implantation. Estrogens secreted by the porcine conceptus on days 11 and 12 of pregnancy provide the initial signal for maternal recognition of pregnancy and maintenance of a functional corpus luteum (CL) for continued production of progesterone. As prostaglandins F2α(PGF2α) and E2(PGE2) exert opposing actions on the CL, a tight control over their synthesis and secretion is critical either for the initiation of luteolysis or maintenance of pregnancy. One of the supportive mechanisms by which conceptus inhibits luteolysis is changing PG synthesis in favor of luteoprotective PGE2. Conceptus PGE2could be amplified by PGE2feedback loop in the endometrium. In pigs, as in other species, implantation and establishment of pregnancy is associated with upregulation of expression of proinflammatory factors, which include cytokines, growth factors, and lipid mediators. The conceptus produces inflammatory mediators: interferon γ and interferon δ, interleukins IL1B and IL6, and PGs, which probably activate inflammatory pathways in the endometrium. The endometrium responds to these embryonic signals by enhancing further progesterone-induced uterine receptivity. Understanding the mechanisms of pregnancy establishment is required for translational research to increase reproductive efficiencies and fertility in humans and animals.

2016 ◽  
Vol 136 (9) ◽  
pp. S257
Author(s):  
G. Cardinali ◽  
D. Kovacs ◽  
V. Maresca ◽  
O. Sasso ◽  
D. Piomelli ◽  
...  

1999 ◽  
Vol 59 (1-6) ◽  
pp. 235
Author(s):  
Hideto Kameda ◽  
John I. Risinger ◽  
Seung Joon Baek ◽  
J. Carl Barrett ◽  
Wayne C. Glasgow ◽  
...  

2000 ◽  
Vol 14 (8) ◽  
pp. 1147-1161 ◽  
Author(s):  
Haengseok Song ◽  
Hyunjung Lim ◽  
Sanjoy K. Das ◽  
Bibhash C. Paria ◽  
Sudhansu K. Dey

Abstract Various mediators, including cytokines, growth factors, homeotic gene products, and prostaglandins (PGs), participate in the implantation process in an autocrine, paracrine, or juxtacrine manner. However, interactions among these factors that result in successful implantation are not clearly understood. Leukemia inhibitory factor (LIF), a pleiotropic cytokine, was shown to be expressed in uterine glands on day 4 morning before implantation and is critical to this process in mice. However, the mechanism by which LIF executes its effects in implantation remains unknown. Moreover, interactions of LIF with other implantation-specific molecules have not yet been defined. Using normal and delayed implantation models, we herein show that LIF is not only expressed in progesterone (P4)-primed uterine glands before implantation in response to nidatory estrogen, it is also induced in stromal cells surrounding the active blastocyst at the time of the attachment reaction. This suggests that LIF has biphasic effects: first in the preparation of the receptive uterus and subsequently in the attachment reaction. The mechanism by which LIF participates in these events was addressed using LIF-deficient mice. We observed that while uterine cell-specific proliferation, steroid hormone responsiveness, and expression patterns of several genes are normal, specific members of the EGF family of growth factors, such as amphiregulin (Ar), heparin-binding EGF-like growth factor (HB-EGF), and epiregulin, are not expressed in LIF(−/−) uteri before and during the anticipated time of implantation, although EGF receptor family members (erbBs) are expressed correctly. Furthermore, cyclooxygenase-2 (COX-2), an inducible rate-limiting enzyme for PG synthesis and essential for implantation, is aberrantly expressed in the uterus surrounding the blastocyst in LIF(−/−) mice. These results suggest that dysregulation of specific EGF-like growth factors and COX-2 in the uterus contributes, at least partially, to implantation failure in LIF(−/−) mice. Since estrogen is essential for uterine receptivity, LIF induction, and blastocyst activation, it is possible that the nidatory estrogen effects in the P4-primed uterus for implantation are mediated via LIF signaling. However, we observed that LIF can only partially resume implantation in P4-primed, delayed implanting mice in the absence of estrogen, suggesting LIF induction is one of many functions that are executed by estrogen for implantation.


2020 ◽  
Author(s):  
Senem Aykul ◽  
Jordan Maust ◽  
Monique Floer ◽  
Erik Martinez-Hackert

ABSTRACTAdipose tissues (AT) expand in response to energy surplus through adipocyte hypertrophy and hyperplasia (i.e., adipogenesis). The latter is a process by which multipotent precursors differentiate into mature adipocytes. This process is directed by growth factors and cytokines, including members of the TGF-β family, which regulate intracellular signaling pathways that control adipogenic transcriptional programs. As ectopic adipogenesis has been linked with metabolic syndrome and other pathological conditions, we undertook to establish how TGF-β family growth factors and their inhibitors regulate this process in a 3T3-L1 adipogenesis model. We found that intracellular SMAD1/5/8 signaling pathways are activated while SMAD2/3 pathways are suppressed in differentiating cells. Addition of SMAD1/5/8 pathway activating ligands promoted cell proliferation, while SMAD2/3 pathway activating ligands suppressed adipocyte formation. We identified several ligand traps that blunted 3T3-L1 adipogenesis. Strikingly, anti-adipogenic traps and ligands exploited the same mechanism of regulation involving a negative feedback loop that links SMAD2/3 activation with SMAD1/5/8 hyper-phosphorylation, cytoplasmic retention, and reduced signaling. The identified anti-adipogenic traps could be used to control hyperplastic AT expansion and its associated pathological conditions.


2009 ◽  
Vol 36 (3) ◽  
pp. 140-148 ◽  
Author(s):  
Jason W. Ross ◽  
Morgan D. Ashworth ◽  
Daniel R. Stein ◽  
Oliver P. Couture ◽  
Christopher K. Tuggle ◽  
...  

Early embryonic development in the pig is characterized by a rapid elongation of the conceptus trophectoderm on days 11–12 of gestation. Initially, the conceptus trophoblast is morphologically rearranged from a 10-mm sphere into a tubular shape, transitioning into a thin filamentous form >150 mm in length in 2–3 h, followed by continued expansion within the uterine lumen for several days. Conceptus elongation is critical for establishing adequate placental surface area needed for embryo and fetal survival throughout gestation. The objective of this study was to characterize conceptus gene expression during trophoblastic elongation and the early attachment to the uterine endometrium on days 11–14 of gestation with the GeneChip Porcine Genome Array. In all, 3,759 different probe sets were statistically different in at least one comparison [spherical vs. tubular, spherical vs. day 12 filamentous (D12F), spherical vs. day 14 filamentous (D14F), tubular vs. D12F, tubular vs. D14F, and D12F vs. D14F]. When restricted to the spherical vs. D12F and D12F vs. D14F comparisons, 482 and 232 genes, respectively, were statistically different with greater than twofold change in expression. Utilization of k-means clustering, in addition to the Database for Annotation, Visualization, and Integrated Discovery (DAVID), identified genes of interest. Quantitative RT-PCR expression profiles for interferon-γ (IFNG), heat shock protein 27 kDa (HSPB1), angiomotin, B-cell linker (BLNK), chemokine ligand 14 (CXCL14), parathyroid hormone-like hormone (PTHLH), and maspin were supportive of the GeneChip Porcine Genome Array data.


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