The Implantation Reaction

Parr, Margaret B.; Parr, Earl L.

doi:10.1007/978-1-4684-5589-2_9

Cited by 95 publications

(64 citation statements)

References 253 publications

(262 reference statements)

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“…The steroid hormones progesterone (P) 2 and estrogen (E) act in concert to control uterine competency for embryo implantation (1). A primary role of P is to induce differentiation of the endometrial stromal cells into morphologically distinct decidual cells (2,3).…”

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“…A primary role of P is to induce differentiation of the endometrial stromal cells into morphologically distinct decidual cells (2,3). In mice, this differentiation process, termed decidualization, is a prerequisite for successful implantation and is initiated at the time of blastocyst attachment to the uterine epithelium on day 4.5 of pregnancy.…”

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“…In mice, this differentiation process, termed decidualization, is a prerequisite for successful implantation and is initiated at the time of blastocyst attachment to the uterine epithelium on day 4.5 of pregnancy. The attachment reaction is followed by the proliferation and differentiation of the stromal cells surrounding the implanting blastocyst to form the decidual bed (2,3). The decidual cells are thought to produce hormones and cytokines that are critical for embryo development, secrete factors that control trophoblast invasion and serve an immunoregulatory function during pregnancy (4,5).…”

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Bone Morphogenetic Protein 2 Functions via a Conserved Signaling Pathway Involving Wnt4 to Regulate Uterine Decidualization in the Mouse and the Human

Kannan

Wang

et al. 2007

Journal of Biological Chemistry

223

228

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A critical role of progesterone (P) during early pregnancy is to induce differentiation of the endometrial stromal cells into specialized decidual cells that support the development of the implanting embryo. The P-induced signaling pathways that participate in the formation and function of the decidual cells remain poorly understood. We report here that the expression of the bone morphogenetic protein 2 (BMP2), a morphogen belonging to the TGF␤ superfamily, is induced downstream of P action in the mouse uterine stroma during decidualization. To determine the function of BMP2 during this differentiation process, we employed a primary culture system in which undifferentiated stromal cells isolated from pregnant mouse uterus undergo decidualization. When recombinant BMP2 was added to these stromal cultures, it markedly advanced the differentiation program. We also found that siRNA-mediated silencing of BMP2 expression in these cells efficiently blocked the differentiation process. Gene expression profiling experiments identified Wnt4 as a downstream target of BMP2 regulation in stromal cells undergoing decidualization. Attenuation of Wnt4 expression by siRNAs greatly reduced stromal differentiation in vitro, indicating that it is a key mediator of BMP2-induced decidualization. We also observed a remarkable induction in the expression of BMP2 in human endometrial stromal cells during decidualization in vitro in response to steroids and cAMP. Addition of BMP2 to these cultures led to a robust enhancement of Wnt4 expression and stimulated the differentiation process. Collectively, our studies uncovered a unique conserved pathway involving BMP2 and Wnt4 that mediates P-induced stromal decidualization in the mouse and the human.The steroid hormones progesterone (P) 2 and estrogen (E) act in concert to control uterine competency for embryo implantation (1). A primary role of P is to induce differentiation of the endometrial stromal cells into morphologically distinct decidual cells (2, 3). In mice, this differentiation process, termed decidualization, is a prerequisite for successful implantation and is initiated at the time of blastocyst attachment to the uterine epithelium on day 4.5 of pregnancy. The attachment reaction is followed by the proliferation and differentiation of the stromal cells surrounding the implanting blastocyst to form the decidual bed (2, 3). The decidual cells are thought to produce hormones and cytokines that are critical for embryo development, secrete factors that control trophoblast invasion and serve an immunoregulatory function during pregnancy (4, 5). However, P-induced signaling molecules that participate in the formation and function of this unique tissue remain poorly understood.It is well established that the majority of the physiological effects of P are mediated via the intracellular progesterone receptors (PRs) (6). Strong evidence in favor of an essential role of PR in P-mediated responses in the uterus came from a mouse model carrying a null mutation of this gene (7). Ablation of P...

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Bone Morphogenetic Protein 2 Functions via a Conserved Signaling Pathway Involving Wnt4 to Regulate Uterine Decidualization in the Mouse and the Human

Kannan

Wang

et al. 2007

Journal of Biological Chemistry

223

228

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“…intrauterine oil infusion) can trigger decidualization. The deciduoma, as it is known, appears very similar to the decidua of normal pregnancy (Parr & Parr 1989). Thus, PS stands as a reliable tool to discriminate between the effects exerted directly on the endometrium or mediated via the embryo.…”

Section: Discussionmentioning

confidence: 91%

Molecular cues to the anti-implantation effect of nano-puerarin in rats

et al. 2016

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Puerarin, a selective oestrogen receptor modulator, intercepts implantation in rats, albeit at unacceptably higher doses. We developed poly lactic-co-glycolic acid-encapsulated nano-puerarin (PN) and mapped the molecular pathway underlying its anti-implantation effects. Smooth-surfaced and spherical PN having a mean diameter of ~147 nm was obtained with good yield, efficient encapsulation, and optimum drug loading. In culture, PN slowly and steadily released puerarin, which was readily taken up by the decidual cells. PN exerted a dose-dependent anti-implantation effect. As marked by attenuated expression of stromal cell desmin, alkaline phosphatase, IGFBP1, and decidual prolactin-related protein, the anti-implantation effect of PN seemed secondary to compromised decidualization. Using in vivo (pregnant and pseudopregnant rats) and in vitro (endometrial stromal cell culture) treatment models, we document that PN enforced inhibition of uterine expression of Hbegf and Hoxa10 and their downstream signalling molecules, Cyclin D3 (CCND3)/CDK4. PN also efficiently ablated the Ihh-Nr2f2-Bmp2 signalling pathway and invited the loss of uterine potential for decidualization. There was a dose-dependent up-regulation of RHOA and its effector protein kinase, ROCK1, leading to the promotion of MLC phosphorylation and actin-myosin interaction. PN also down-regulated the stromal cell activation of ERK½ and expression of MMP9. These effects acting together stabilized the stroma and inhibited the stromal cell migration. Central to this array of events was the adversely altered endometrial expression of oestrogen receptor subtypes and repression of progesterone receptor that indulged endless proliferation of luminal epithelia and distorted the precisely choreographed stroma-epithelia crosstalk. Thus, PN dismantles the endometrial bed preparation and prevents implantation.Reproduction (2016) 151 693-707

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“…The endometrial fibroblasts of rodents and humans undergo remarkable morphological and functional modifications while transforming into decidual cells during the early stages of pregnancy (reviews in Parr and Parr, 1989;Abrahamsohn and Zorn, 1993). In rodents the stimulus for the decidual reaction is provided by the embryo, although a similar phenomenon can be induced artificially by appropriate stimulation of the uterus (see De Feo, 1967).…”

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confidence: 99%