Diverse Roles of Prostaglandins in Blastocyst Implantation

Salleh, Naguib

doi:10.1155/2014/968141

Cited by 62 publications

(53 citation statements)

References 158 publications

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“…In addition to Itga4, many other plasma membrane receptors exhibited altered expression levels in uterine GR KO mice. Prostaglandins also have an important role as signaling molecules in the early events of implantation and decidualization, and both prostaglandin I2 receptor (Ptgir) and prostaglandin E receptor 4 (Ptger4) were down-regulated in uterine GR KO mice following the decidualization stimulus (19). Although neither of these genes has been previously shown to be regulated by glucocorticoids, we found that Ptgir was significantly regulated by dexamethasone in our microarray in the uterus of control mice.…”

Section: Discussionmentioning

confidence: 55%

Uterine glucocorticoid receptors are critical for fertility in mice through control of embryo implantation and decidualization

Whirledge

Oakley

Myers

et al. 2015

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

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In addition to the well-characterized role of the sex steroid receptors in fertility and reproduction, organs of the female reproductive tract are also regulated by the hypothalamic-pituitary-adrenal axis. These endocrine organs are sensitive to stress-mediated actions of glucocorticoids, and the mouse uterus contains high levels of the glucocorticoid receptor (GR). Although the presence of GR in the uterus is well established, uterine glucocorticoid signaling has been largely ignored in terms of its reproductive and/or immunomodulatory functions on fertility. To define the direct in vivo function of glucocorticoid signaling in adult uterine physiology, we generated a uterine-specific GR knockout (uterine GR KO) mouse using the PR cre mouse model. The uterine GR KO mice display a profound subfertile phenotype, including a significant delay to first litter and decreased pups per litter. Early defects in pregnancy are evident as reduced blastocyst implantation and subsequent defects in stromal cell decidualization, including decreased proliferation, aberrant apoptosis, and altered gene expression. The deficiency in uterine GR signaling resulted in an exaggerated inflammatory response to induced decidualization, including altered immune cell recruitment. These results demonstrate that GR is required to establish the necessary cellular context for maintaining normal uterine biology and fertility through the regulation of uterine-specific actions.glucocorticoid receptor | uterus | decidualization | implantation

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Section: Discussionmentioning

confidence: 55%

Uterine glucocorticoid receptors are critical for fertility in mice through control of embryo implantation and decidualization

Whirledge

Oakley

Myers

et al. 2015

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

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“…Furthermore, the pattern of COX-2 expression in the pregnant rat uterus suggests a fundamental role during embryo implantation and decidualization [4,5]. In animal models, PG signaling has been implicated in increased vascular permeability, stromal decidualization, embryo development, and extracellular matrix remodeling during implantation [3]. However, in humans, till now little is known about the role of PGs in decidualization.…”

Section: Discussionmentioning

confidence: 99%

“…PGs, derived from cyclooxygenase-2 (COX-2), are believed to play an important role in regulating decidualization, angiogenesis, vascular remodeling, trophoblast invasion, and extracellular matrix remodeling during implantation [3]. In rats, COX-2 expression is mostly restricted to implantation sites, and COX-2 2/2 mice are infertile, with defective implantation and decidualization [4,5].…”

Section: Introductionmentioning

confidence: 99%

Anandamide interferes with human endometrial stromal‐derived cell differentiation: An effect dependent on inhibition of cyclooxygenase‐2 expression and prostaglandin E₂ release

et al. 2016

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SummaryThe human endometrium undergoes cyclical growth, differentiation, and regression periods throughout the reproductive life. The process in which endometrial stromal cells proliferate and differentiate into decidual cells, named decidualization, prepares a receptive endometrium for implantation. Prostaglandins (PGs) and endocannabinoids (eCBs) are crucial mediators of this process. We have recently reported that the eCB anandamide (AEA) interferes with rat stromal cell differentiation, and on the other hand, PGs are also crucial for decidualization. Therefore, in this study, we analyzed the AEA levels, both in nondifferentiated and in decidualizing human endometrial stromal cells by liquid chromatography‐mass spectrometry, and investigated the impact of AEA on PG release and cyclooxygenase‐2 (COX‐2) expression in human endometrial stromal‐derived cell differentiation. For that, an ultra‐performance liquid chromatography‐mass spectrometry/mass spectrometry method to measure prostaglandin E2 (PGE2) and prostaglandin F2α in biological samples was developed and validated. We demonstrate that AEA levels in decidualizing cells are lower than those in nondifferentiated cells, whereas PGE2 levels and COX‐2 expression are up‐regulated. Thus, low AEA levels may be essential for the onset of decidualization. On the contrary, in AEA‐treated cells undergoing decidualization, a decrease of COX‐2 protein levels and PGE2 production, in a manner dependent on cannabinoid receptor 1 activation, was observed. Overall, these findings suggest that a deregulation of the intricate network that drives cell differentiation may compromise pregnancy and fertility. It is clinically relevant to understand the mechanisms that influence eCB and PG levels in the endometrium because they may shed light on the sequence of events that lead to a successful pregnancy. © 2016 BioFactors, 42(3):277–286, 2016

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“…These findings suggested that in estrogen pretreated uteri, other factors, for example, LIF (Salleh and Giribabu 2014) and prostaglandins (PGs) (Salleh 2014) could be involved in controlling V-ATPase expression under progesterone influence. These paracrine regulations could help to optimize the pH needed for embryo implantation.…”

Section: Discussionmentioning

confidence: 99%

Vacuolar-ATPase (V-ATPase) Mediates Progesterone-Induced Uterine Fluid Acidification in Rats

et al. 2015

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We hypothesized that progesterone-induced decrease in uterine fluid pH involves V-ATPase. In this study, expression and functional activity of V-ATPase in uterus were investigated under progesterone influence. Ovariectomized adult female rats received subcutaneous injection of estradiol-17β (1 µg/kg/day) or progesterone (20 mg/kg/day) for 3 days or 3 days estradiol-17β followed by 3 days vehicle, progesterone, or estradiol-17β plus progesterone. Mifepristone, a progesterone receptor blocker, was concomitantly given to the rats which received progesterone. A day after last injection, rate of uterine fluid secretion, its HCO3 (-) concentration, and pH were determined via in vivo uterine perfusion in rats under anesthesia. V-ATPase inhibitor, bafilomycin, was introduced into the perfusion buffer, and changes in these parameters were observed. Expression of V-ATPase A1 and B1/2 proteins and mRNAs in uterus were quantified by Western blotting and real-time PCR, respectively. Distribution of these proteins was observed by immunohistochemistry. Our findings showed that under progesterone influence, uterine fluid secretion rate, HCO3 (-) concentration, and pH were significantly reduced. Administration of bafilomycin did not cause significant changes in fluid secretion rate; however, HCO3 (-) concentration and pH were significantly elevated. In parallel with these changes, expression of V-ATPase A1 and B1/2 proteins and mRNAs were significantly increased with these proteins highly distributed in uterine luminal and glandular epithelia. In conclusion, increased expression and functional activity of V-ATPase were most likely responsible for the decreased in uterine fluid pH observed under progesterone influence.

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Diverse Roles of Prostaglandins in Blastocyst Implantation

Cited by 62 publications

References 158 publications

Uterine glucocorticoid receptors are critical for fertility in mice through control of embryo implantation and decidualization

Uterine glucocorticoid receptors are critical for fertility in mice through control of embryo implantation and decidualization

Anandamide interferes with human endometrial stromal‐derived cell differentiation: An effect dependent on inhibition of cyclooxygenase‐2 expression and prostaglandin E₂ release

Vacuolar-ATPase (V-ATPase) Mediates Progesterone-Induced Uterine Fluid Acidification in Rats

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Diverse Roles of Prostaglandins in Blastocyst Implantation

Cited by 62 publications

References 158 publications

Uterine glucocorticoid receptors are critical for fertility in mice through control of embryo implantation and decidualization

Uterine glucocorticoid receptors are critical for fertility in mice through control of embryo implantation and decidualization

Anandamide interferes with human endometrial stromal‐derived cell differentiation: An effect dependent on inhibition of cyclooxygenase‐2 expression and prostaglandin E2 release

Vacuolar-ATPase (V-ATPase) Mediates Progesterone-Induced Uterine Fluid Acidification in Rats

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Anandamide interferes with human endometrial stromal‐derived cell differentiation: An effect dependent on inhibition of cyclooxygenase‐2 expression and prostaglandin E₂ release