Cyclo-oxygenase-2-derived prostacyclin mediates embryo implantation in the mouse via PPARdelta

Lim, Hyunjung Jade; Gupta, Rajnish A.; Ge, Wen; Paria, Bibhash C.; Moller, David E.; Morrow, Jason D.; DuBois, Raymond N.; Trzaskos, James M.; Dey, Sudhansu K.

doi:10.1101/gad.13.12.1561

Cited by 560 publications

(394 citation statements)

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“…It was demonstrated that PPARg and PPARd/b are key mediators of normal blastocyst implantation and elongation in early gestation and it has been shown that COX2 mediates embryo implantation in the mouse via PPARd/b (Lim et al, 1999;Huang, 2008). Taken altogether, these results indicate a link between the type of omega (3 v. 6) FA present in the diet, the type of prostaglandins synthesised (series 2 v. 3), and the expression of genes involved in reproduction.…”

Section: Fas Antioxidants and Reproductive Performancementioning

confidence: 88%

“…Therefore, strategies to further inhibit secretion of series 2 prostaglandins may result in increased embryonic survival and pregnancy rates. The production of endometrial series 2 prostaglandins is mainly governed by the rate-limiting enzyme cyclooxygenase (COX)-2, which mediates embryo implantation in the mouse (Lim et al, 1999;Huang, 2008). The most potent COX-2 inhibitor is an omega 3 FA, eicosapentanoic acid (Ringbom et al, 2001).…”

Section: Fas Antioxidants and Reproductive Performancementioning

confidence: 99%

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Nutritional sub-fertility in the dairy cow: towards improved reproductive management through a better biological understanding

Friggens

Disenhaus

Petit

2010

Animal

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There has been a significant decline in the reproductive performance of dairy cattle in recent decades. Cows, take longer time to return to the oestrus after calving, have poorer conception rates, and show fewer signs of oestrus. Achieving good reproductive performance is an increasing challenge for the dairy producer. In this study we focus on understanding the overall biological phenomena associated with nutritional sub-fertility rather than the underlying multiplicity of physiological interactions (already described in a number of recent studies). These phenomena are important because they represent the natural adaptations of the animal for dealing with variations in the nutritional environment. They can also be used to monitor and modulate reproductive performance on-farm. There is an underlying trade-off between two aspects of reproduction: investment in the viability of the current calf and investment in future offspring. As the investment in, and viability of, the current calf is related to maternal milk production, we can expect that level of milk production per se has effects on subsequent reproductive performance (investment in future offspring). Lactating cows have a lower proportion of viable embryos, which are of poorer quality, than do non-lactating cows. The same applies to high-compared to medium-genetic merit cows. Another important biological property is the adaptive use of body reserves in support of reproduction. Orchestrated endocrine changes in pregnancy and lactation facilitate the deposition of body lipid during pregnancy and mobilisation in early lactation. When the cow fails to accumulate the reserves she needs to safeguard reproduction she delays committing to further reproductive investment. But how does the cow 'know' that she is failing in energy terms? We argue that the cow does this by 'monitoring' both the body fat mobilisation and body fatness. Excessive body fat mobilisation indicates that current conditions are worse than expected. Body fatness indicates the future ability of the cow to safeguard her reproductive investment is compromised. Both delay further reproductive commitment. The relationship between reproductive performance and; milk production as an index of maternal investment, body fatness as an index of ability to safeguard reproductive investment, and body fat mobilisation as an index of the current nutritional environment -are examined. Nutritional strategies that seek to modulate body mobilisation and the endocrine environment by use of glucogenic and lipogenic diets, and the use of in-line progesterone profiles to monitor reproductive status are then discussed in this biological context.

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Section: Fas Antioxidants and Reproductive Performancementioning

confidence: 88%

Section: Fas Antioxidants and Reproductive Performancementioning

confidence: 99%

Nutritional sub-fertility in the dairy cow: towards improved reproductive management through a better biological understanding

Friggens

Disenhaus

Petit

2010

Animal

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“…Alternatively, the perinuclear PGE 2 (or possibly other unknown metabolites) produced by COX-2/mPGES-1 may act on certain nuclear receptors that in turn promote cell growth. Indeed, several eicosanoids have been shown to stimulate the peroxisome proliferator-activated receptor family of nuclear receptors (43,44). Nonetheless, different sensitivity of PGE 2 production by HCA-7 cells to COX-2 and mPGES-1 inhibitors and mPGES-1 antisense oligonucleotide strongly argues that this cell line may contain an alternative COX-2-dependent PGE 2 -biosynthetic route that involves other PGES enzyme(s).…”

Section: Mpges-1 and Tumorigenesismentioning

confidence: 98%

Potential Role of Microsomal Prostaglandin E Synthase-1 in Tumorigenesis

Kamei

Murakami

Nakatani

et al. 2003

Journal of Biological Chemistry

181

168

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Microsomal prostaglandin E 2 synthase-1 (mPGES-1) is a stimulus-inducible enzyme that functions downstream of cyclooxygenase (COX)-2 in the PGE 2 -biosynthetic pathway. Given the accumulating evidence that COX-2-derived PGE 2 participates in the development of various tumors, including colorectal cancer, we herein examined the potential involvement of mPGES-1 in tumorigenesis. Immunohistochemical analyses demonstrated the expression of both COX-2 and mPGES-1 in human colon cancer tissues. HCA-7, a human colorectal adenocarcinoma cell line that displays COX-2-and PGE 2 -dependent proliferation, expressed both COX-2 and mPGES-1 constitutively. Treatment of HCA-7 cells with an mPGES-1 inhibitor or antisense oligonucleotide attenuated, whereas overexpression of mPGES-1 accelerated, PGE 2 production and cell proliferation. Moreover, cotransfection of COX-2 and mPGES-1 into HEK293 cells resulted in cellular transformation manifested by colony formation in soft agar culture and tumor formation when implanted subcutaneously into nude mice. cDNA array analyses revealed that this mPGES-1-directed cellular transformation was accompanied by changes in the expression of a variety of genes related to proliferation, morphology, adhesion, and the cell cycle. These results collectively suggest that aberrant expression of mPGES-1 in combination with COX-2 can contribute to tumorigenesis.Clinical, genetic, and biochemical evidence has suggested that prostaglandin (PG) 1 E 2 produced via the cyclooxygenase (COX)-2-dependent pathway plays a crucial role in the development of colorectal cancer and possibly other cancers (1). Non-steroidal anti-inflammatory drugs, which inhibit COX-2, reduce the incidence of colorectal cancer (2-4). The major prostanoid produced by several types of cancer is PGE 2 , which is produced by three biosynthetic reactions involving phospholipase A 2 (PLA 2 ), COX, and terminal PGE 2 synthase (PGES). PGE 2 promotes survival and motility of colon cancer cells in vitro and promotes tumorigenesis and angiogenesis in vivo (5-7). High levels of constitutive expression of COX-2 have been found in various cancer cells and tissues (8,9), and studies employing overexpression, antisense suppression, and specific inhibitors of COX-2 have demonstrated that COX-2 contributes to the progression of several types of cancer (10 -12).More direct evidence for the role of COX-2 and its product PGE 2 in colorectal tumorigenesis has been provided by gene targeting studies. Gene disruption of either COX-2 (13) or the PGE receptor EP2 (14) results in reduction of the number and size of intestinal polyps in Apc mutant mice, a model for human familial adenomatous polyposis. In another model, disruption of the genes for the PGE receptors EP1 (15) or EP4 (16) suppresses the development of colorectal cancer induced by carcinogen. Moreover, gene knockout of cytosolic PLA 2 ␣ (cPLA 2 ␣), which supplies the substrate arachidonic acid to COX-2, also leads to reduced polyposis in Apc mutant mice (17,18).PGES catalyzes the conversion of PGH 2 ...

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“…It is also unknown whether or not Ptgis is also expressed at the implantation site of hamsters as reported previously in mice (17). One way to address these concerns is by co-localization of Ptgs2 and PGE 2 -or PGI 2 -synthesizing enzymes at the same location of implantation sites.…”

Section: Fig 5 Peri-implantation (Daysmentioning

confidence: 99%

“…PGE 2 may also have immunomodulatory roles at the implantation site (15). Recently, it has been demonstrated in the mouse that uterine PGE 2 and PGI 2 are important for ovulation and initiation of implantation, respectively (16,17). In contrast, Kennedy (18) showed that in the rat PGE 2 but not PGI 2 is a key mediator of increased vascular permeability at the implantation site.…”

mentioning

confidence: 99%

Prostaglandin E2 Is a Product of Induced Prostaglandin-endoperoxide Synthase 2 and Microsomal-type Prostaglandin E Synthase at the Implantation Site of the Hamster

Wang¹,

Su²,

Deb³

et al. 2004

Journal of Biological Chemistry

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Certain uterine prostaglandins (PGs) are elevated at implantation sites and are needed to trigger the events of blastocyst implantation that include blastocyst-uterine attachment and stromal decidualization with vascular permeability changes. Several decades of investigations showed that treatment with PG synthesis inhibitors, prior to or during the time of implantation, resulted in either complete inhibition or a delay in implantation or reduction in the number of implantation sites with diminished decidual tissue. Consistent with these findings, we observed that whereas a selective PG endoperoxide synthase (Ptgs) 1 inhibitor SC-560 failed to inhibit implantation, a selective Ptgs2 inhibitor SC-236 showed significantly reduced number and size of implantation sites in progesterone-treated ovariectomized pregnant hamsters. It is known that Ptgs2 expression and Ptgs2-derived prostacyclin (PGI 2 ) synthesis at implantation sites are needed for implantation in the mouse (a rodent that needs ovarian estrogen for implantation). However, it is unknown which Ptgs and PG synthases produce which PGs at implantation sites of the hamster (a rodent that does not need ovarian estrogen for implantation). Here we demonstrate that as blastocyst implantation proceeds, a reduction in Ptgs1 expression from uterine luminal epithelial cells and a gradual induction in Ptgs2 expression exclusively in luminal epithelial and adjacent decidual cells occurred at implantation sites of hamsters. Results also reveal that PGE 2 , but not PGI 2 , is the major PG at implantation sites where Ptgs2 and microsomal type PGE synthases but not PGI synthases are co-expressed. This elevated uterine PGE 2 at implantation sites may serve to initiate or amplify physiological signals required for specific aspects of the implantation process in hamsters.

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Cyclo-oxygenase-2-derived prostacyclin mediates embryo implantation in the mouse via PPARdelta

Cited by 560 publications

References 76 publications

Nutritional sub-fertility in the dairy cow: towards improved reproductive management through a better biological understanding

Nutritional sub-fertility in the dairy cow: towards improved reproductive management through a better biological understanding

Potential Role of Microsomal Prostaglandin E Synthase-1 in Tumorigenesis

Prostaglandin E2 Is a Product of Induced Prostaglandin-endoperoxide Synthase 2 and Microsomal-type Prostaglandin E Synthase at the Implantation Site of the Hamster

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