Delayed Implantation in the Spayed, Progesterone Treated Adult Mouse

Yoshinaga, Koji; Adams, C. E.

doi:10.1530/jrf.0.0120593

Cited by 237 publications

(138 citation statements)

References 6 publications

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“…These responses include the blastocyst-uterine attachment reaction, uterine vascular permeability changes, and stromal decidualization (23). Evidence for these PG responses was further supported by mutation of Ptgs2 in the mouse (12,13), where implantation occurs in response to ovarian estrogen (24,25). Ovarian estrogen is not a requirement for initiation of implantation in certain species including hamsters, rabbits, pigs, monkeys, and perhaps humans (26 -36).…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

“…In mice and rats, maternal estrogen is essential to initiate the process of blastocyst implantation in a P 4 -primed uterus (23)(24)(25). In contrast, maternal estrogen is not required to initiate the process of implantation in the P 4 -primed uterus in hamsters, rabbits, pigs, guinea pigs, monkeys, and perhaps in humans (26 -36).…”

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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“…We sought to address the mechanism of differential effects of anandamide in blastocyst function and implantation. We first examined whether anandamide at varying levels differentially influences MAPK signaling in blastocysts undergoing experimentally induced dormancy (18,26,27). We observed that anandamide at 7 nM rapidly induced phosphorylation of ERK and its translocation into nuclei of trophectoderm cells of dormant blastocysts within 5 min, showing a peak between 15 and 30 min (Fig.…”

Section: Anandamide Rapidly Activates Erk Signaling In Blastocysts In Amentioning

confidence: 99%

“…Preimplantation ovarian estrogen secretion on day 4 of pregnancy is essential for implantation. This process is deferred if ovaries are removed before the preimplantation estrogen secretion, resulting in delayed implantation that can be main- tained for many days by continued P 4 treatment with the uterus remaining in a quiescent state and blastocysts in dormancy (18,26,27). Dormant blastocysts, if cultured in vitro, gain metabolic competence (29).…”

Section: Anandamide At Low Concentration Confers Blastocyst Competencmentioning

confidence: 99%

Differential G protein-coupled cannabinoid receptor signaling by anandamide directs blastocyst activation for implantation

Wang

Matsumoto

Guo

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

141

113

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Mammalian fertility absolutely depends on synchronized development of the blastocyst to the stage when it is competent to implant, and the uterus to the stage when it is receptive to implantation. However, the molecular basis for the reciprocal interaction between the embryo and the uterus remains largely unexplored. One potentially important mechanism involves signaling between an evolutionarily conserved G protein-coupled protein cannabinoid receptor, CB1, that is expressed at high levels on the surface of the trophectoderm and anandamide (N-arachidonoylethanolamine), an endocannabinoid ligand found to be produced at higher levels by the uterus before implantation and then down-regulated at the time of implantation. Using genetic, pharmacological, and physiological approaches, we show here that anandamide within a very narrow range regulates blastocyst function and implantation by differentially modulating mitogenactivated protein kinase signaling and Ca 2؉ channel activity via CB1 receptors. Anandamide at a low concentration (7 nM) induces extracellular regulated kinase phosphorylation and nuclear translocation in trophectoderm cells without influencing Ca 2؉ channels, and renders the blastocyst competent for implantation in the receptive uterus. In contrast, anandamide at a higher concentration (28 nM) inhibits Ca 2؉ channel activity and blastocyst competency for implantation without influencing mitogen-activated protein kinase signaling. Besides uncovering a potentially important regulatory mechanism for synchronizing blastocyst and uterine competency to implantation, this observation has high clinical relevance, because elevated levels of anandamide induce spontaneous pregnancy loss in women.

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“…This condition, referred as delayed implantation, can be maintained by continued P 4 treatment. However, implantation with blastocyst activation rapidly occurs by an estrogen injection in P 4 -primed mice (3,4). Delayed implantation also occurs naturally (facultative) during lactation after postpartum ovulation and successful mating in mice; implantation occurs after termination of the suckling stimulus (5).…”

mentioning

confidence: 99%

Global gene expression analysis identifies molecular pathways distinguishing blastocyst dormancy and activation

Hamatani

Daikoku

Wang

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

231

234

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Delayed implantation (embryonic diapause) occurs when the embryo at the blastocyst stage achieves a state of suspended animation. During this period, blastocyst growth is very slow, with minimal or no cell division. Nearly 100 mammals in seven different orders undergo delayed implantation, but the underlying molecular mechanisms that direct this process remain largely unknown. In mice, ovariectomy before preimplantation ovarian estrogen secretion on day 4 of pregnancy initiates blastocyst dormancy, which normally lasts for 1-2 weeks by continued progesterone treatment, although blastocyst survival decreases with time. An estrogen injection rapidly activates blastocysts and initiates their implantation in the progesterone-primed uterus. Using this model, here we show that among Ϸ20,000 genes examined, only 229 are differentially expressed between dormant and activated blastocysts. The major functional categories of altered genes include the cell cycle, cell signaling, and energy metabolic pathways, particularly highlighting the importance of heparin-binding epidermal growth factor-like signaling in blastocyst-uterine crosstalk in implantation. The results provide evidence that the two different physiological states of the blastocyst, dormancy and activation, are molecularly distinguishable in a global perspective and underscore the importance of specific molecular pathways in these processes. This study has identified candidate genes that provide a scope for in-depth analysis of their functions and an opportunity for examining their relevance to blastocyst dormancy and activation in numerous other species for which microarray analysis is not available or possible due to very limited availability of blastocysts.S uccessful implantation results from reciprocal interactions between an implantation-competent blastocyst and a receptive uterus. Highly coordinated cellular and molecular events, directed by ovarian estrogen and progesterone (P 4 ), produce a favorable uterine environment, the receptive state, to support implantation. The blastocyst also functions as an active unit with its own molecular program of cell growth and differentiation (1, 2). It is difficult to distinguish embryonic and uterine events during normal pregnancy with respect to blastocyst activation and uterine receptivity because of the changing levels of ovarian hormones. Because estrogen is essential for on-time uterine receptivity and blastocyst activation in mice (3), ovariectomy before preimplantation estrogen secretion on the morning of day 4 results in implantation failure, initiating a state of blastocyst dormancy. This condition, referred as delayed implantation, can be maintained by continued P 4 treatment. However, implantation with blastocyst activation rapidly occurs by an estrogen injection in P 4 -primed mice (3, 4). Delayed implantation also occurs naturally (facultative) during lactation after postpartum ovulation and successful mating in mice; implantation occurs after termination of the suckling stimulus (5). Lactational delay ...

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Delayed Implantation in the Spayed, Progesterone Treated Adult Mouse

Cited by 237 publications

References 6 publications

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

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

Differential G protein-coupled cannabinoid receptor signaling by anandamide directs blastocyst activation for implantation

Global gene expression analysis identifies molecular pathways distinguishing blastocyst dormancy and activation

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