Myometrium and Preterm Labor: Steroids and Prostaglandins

Myatt, Leslie; Moore, S. D.

doi:10.1055/s-2007-1016410

Cited by 11 publications

(8 citation statements)

References 74 publications

(105 reference statements)

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“…Therefore the priming interaction of P 4 and estrogen in the endometrium seems to be subtype specific and is mediated by the ESR1 receptor. In the uterus, P 4 is known to negatively regulate the expression of ESR1, and P 4 withdrawal results in an induction of ESR1 expression (38,55). In pregnant sheep P 4 alone upregulated cervical ESR1 mRNA, and E 2 stimulated ESR1 mRNA expression only after sufficient P 4 priming (54).…”

Section: Discussionmentioning

confidence: 99%

Actions and interactions of progesterone and estrogen on transcriptome profiles of the bovine endometrium

Shimizu

Krebs

Bauersachs

et al. 2010

Physiological Genomics

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The aim of our study was to analyze endometrial gene expression profiles in ovariectomized cows treated with estradiol and/or progesterone by using microarray analysis. Clustering of differentially expressed genes allowed separation into distinct hormone response patterns. These patterns could be classified into independent and interdependent actions of the steroid hormones estrogen and progesterone. The use of ovariectomized cows and external administration of hormones identified a set of genes whose regulation depends on a progesterone priming effect. The progesterone-primed estrogen response comprises gene functions such as migration, cell differentiation, and cell adhesion and therefore may play a crucial role in tissue remodeling, as one of its key regulators in the endometrium, TGFB2, is among this group of progesterone-primed genes. Functional annotation analysis of the estrogen-responsive gene clusters shows a clear dominance of functions such as cell cycle, morphogenesis, and differentiation. The functional profile of the progesterone-responsive clusters is less clear but nevertheless shows some important fertility-related terms like luteinization, oocyte maturation, and catecholamine metabolism. We looked for putative regulators of the steroid hormone response in endometrium by searching for enriched transcription factor binding sites in the promoter regions of the genes with similar hormone response profile. This analysis identified transcription factors such as SP1, NFYA, FOXA2, IRF2, ESR1, and NOBOX as candidate regulators of gene expression in bovine endometrium treated with steroid hormones. Taken together, our data provide novel insights into the regulation of bovine endometrial physiology by steroid hormones.

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Section: Discussionmentioning

confidence: 99%

Actions and interactions of progesterone and estrogen on transcriptome profiles of the bovine endometrium

Shimizu

Krebs

Bauersachs

et al. 2010

Physiological Genomics

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“…In addition to inducing the key enzyme responsible for the production of cervical PG, additional priming with progesterone at 0.7 gestations before stimulation with estradiol also enhanced PTGER4 expression, a relaxing subtype of PGE 2 receptor [15][16][17][18]. Parallel evaluation of PTGER2 receptor, the other relaxant receptor of PGE 2 , was also performed.…”

Section: Discussionmentioning

confidence: 99%

“…At least four receptors (PTGER 1-4) encoded by separate genes exist for PGE 2 [15][16][17][18]. These four receptors work through multiple second messenger systems to produce different downstream events and determine the tissue-specific response to PGE 2 .…”

Section: Introductionmentioning

confidence: 99%

“…These four receptors work through multiple second messenger systems to produce different downstream events and determine the tissue-specific response to PGE 2 . PTGER1 and PTGER3 receptors are coupled to calcium mobilization and inhibition of adenylate cyclase, respectively, both of which enhance smooth muscle contraction [15][16][17][18]. In contrast, PTGER2 (also known as EP2) and PTGER4 (also known as EP4) receptors both stimulate adenylate cyclase [15][16][17][18] and tend to decrease smooth muscle contractility.…”

Section: Introductionmentioning

confidence: 99%

“…PTGER1 and PTGER3 receptors are coupled to calcium mobilization and inhibition of adenylate cyclase, respectively, both of which enhance smooth muscle contraction [15][16][17][18]. In contrast, PTGER2 (also known as EP2) and PTGER4 (also known as EP4) receptors both stimulate adenylate cyclase [15][16][17][18] and tend to decrease smooth muscle contractility. Of the four subtype receptors, PTGER2 and PTGER4 are the most likely receptors responsible for PGE 2 -induced cervical ripening and dilation because a softened, relaxed, and dilated cervix is required for fetal delivery.…”

Section: Introductionmentioning

confidence: 99%

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Sufficient Progesterone-Priming Prior to Estradiol Stimulation Is Required for Optimal Induction of the Cervical Prostaglandin System in Pregnant Sheep at 0.7 Gestations1

Wen¹,

Coksaygan²,

Chakrabarty³

et al. 2005

Biology of Reproduction

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The purposes of this study were to determine the separate and interactive functions of progesterone and estradiol in regulating the cervical prostaglandin (PG) system in pregnant sheep at 0.7 gestations. At 106-108 days of gestational age (dGA), ewes were treated with vehicle for 14 days (n = 5) or vehicle for 12 days followed by estradiol 5 mg twice a day, intramuscularly for 2 days (n = 5) or progesterone 100 mg, twice a day, intramuscularly for 14 days (n = 5) or progesterone 100 mg twice a day, intramuscularly for 10 days and then 2 days vehicle followed by estradiol 5 mg twice a day intramuscularly for 2 days (n = 5). At 121-123 dGA, cervical tissues were obtained under halothane anesthesia. Cervical RNA and protein were extracted and analyzed for prostaglandin-endoperoxide synthase 2 (COX2), two PGE(2) receptors, PTGER2 and PTGER4, and estrogen receptor alpha (ESR1) by Northern and Western blot analysis. Immunocytochemistry and in situ hybridization were applied to localize cellular distribution of COX2, PTGER2, and PTGER4 in the cervix. Data were analyzed by ANOVA. COX2 and PTGER4 mRNAs and proteins were increased (P < 0.05) in ewes treated with combined estradiol and progesterone but not in ewes treated with estradiol or progesterone alone compared with controls. ESR1 mRNA was increased in ewes treated with progesterone and estradiol plus progesterone. In contrast, PTGER2 mRNA and protein remained the same after all treatments. COX2 mRNA and protein were localized only in cervical glandular epithelial cells, whereas PTGER2 and PTGER4 were localized in both cervical glandular epithelial and smooth muscle cells. In conclusion, these data suggest that additional progesterone priming at 0.7 gestations synergizes with estradiol to induce cervical COX2, PTGER4, and ESR1 and support our hypothesis that stimulation of the cervical PG system by estradiol is optimized by sufficient progesterone priming in the pregnant sheep cervix.

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Do uterine PTGS2, PGFS, and PTGFR expression play a role in canine uterine inertia?

et al. 2021

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The aetiology of primary uterine inertia (PUI), which is the most common cause of canine dystocia, is still not elucidated. Prostaglandins (PGs) play a crucial role in parturition. We hypothesized that the expression of prostaglandin endoperoxidase synthase 2 (PTGS2), PGF2α synthase (PGFS), and corresponding receptor (PTGFR) is altered in PUI. We investigated PTGS2, PGFS, and PTGFR mRNA expression, and PTGS2 and PGFS protein expression in interplacental (IP) and uteroplacental sites (UP) in bitches with PUI, obstructive dystocia (OD), and prepartum (PC). PTGS2, PGFS, and PTGFR mRNA expression did not differ significantly between PUI and OD (IP/UP). PTGFR ratio in UP was higher in PC than in OD (p = 0.014). PTGS2 immunopositivity was noted in foetal trophoblasts, luminal and superficial glandular epithelial cells, smooth muscle cells of both myometrial layers, and weakly and sporadically in deep uterine glands. PGFS was localized in luminal epithelial cells and in the epithelium of superficial uterine glands. PTGS2 and PGFS staining was similar between PUI and OD, while PGFS protein expression differed between OD and PC (p = 0.0215). For PTGS2, the longitudinal myometrial layer of IP stained significantly stronger than the circular layer, independent of groups. These results do not support a role for PTGS2, PGFS, and PTGFR in PUI. Reduced PGFS expression in IP during parturition compared with PC and the overall lack of placental PGFS expression confirm that PGFS is not the main source of prepartal PGF2alpha increase. The difference in PTGS2 expression between IP myometrial layers warrants further investigation into its physiological relevance.

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Myometrium and Preterm Labor: Steroids and Prostaglandins

Cited by 11 publications

References 74 publications

Actions and interactions of progesterone and estrogen on transcriptome profiles of the bovine endometrium

Actions and interactions of progesterone and estrogen on transcriptome profiles of the bovine endometrium

Sufficient Progesterone-Priming Prior to Estradiol Stimulation Is Required for Optimal Induction of the Cervical Prostaglandin System in Pregnant Sheep at 0.7 Gestations1

Do uterine PTGS2, PGFS, and PTGFR expression play a role in canine uterine inertia?

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