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Canine Placental Prostaglandin E2 Synthase (PTGES): Expression, Localization, and Biological Functions in Providing Substrates for Prepartum PGF2alpha Synthesis


Gram, Aykut; Fox, Barbara; Büchler, Urs; Boos, Alois; Hoffmann, Bernd; Kowalewski, Mariusz P (2014). Canine Placental Prostaglandin E2 Synthase (PTGES): Expression, Localization, and Biological Functions in Providing Substrates for Prepartum PGF2alpha Synthesis. Biology of Reproduction, 91(6):154.

Abstract

The prepartum output of PGF2alpha in the bitch is associated with increased placental PGE2-synthase (PTGES)-mRNA levels. Contrasting with this is a decreased expression of PGF2alpha-synthase (PGFS/AKR1C3) in utero-placental compartments during prepartum luteolysis, suggesting an involvement of alternative synthetic pathways in PGF2alpha synthesis, e.g., conversion of PGE2 to PGF2alpha. However, since the expression and possible functions of the respective PTGES protein remained unknown, no further conclusion could be drawn. Therefore, a canine-specific PTGES antibody was generated and used to investigate the expression, cellular localization and biochemical activities of canine utero-placental PTGES throughout pregnancy and at prepartum luteolysis. Additionally, the biochemical activities of these tissues involved in the conversion of PGE2 to PGF2alpha were investigated. The endometrial PTGES was localized in the uterine surface epithelium pre-implantation, and in superficial and deep uterine glands, endothelial cells and myometrium throughout pregnancy and at parturition. Placental signals were mostly in the trophoblast. The biochemical properties of recombinant PTGES protein were confirmed. Additionally, expression of two PGE2-receptors, PTGER2/EP2 and PTGER4/EP4, revealed their decreasing expression during luteolysis. In contrast, the utero-placental expression of prostaglandin transporter (PGT) was strongly elevated prior to parturition. These localization patterns resembled that of PTGES. The increased expression of PTGES and PGT at parturition, together with the accompanying decreased levels of PGE2-receptors, and the capability of canine uterine and placental homogenates to take part in the conversion of PGE2 to PGF2alpha, as found in this study, suggest that PGE2 could be utilized locally as a substrate for prepartum PGF2alpha synthesis in the dog.

Abstract

The prepartum output of PGF2alpha in the bitch is associated with increased placental PGE2-synthase (PTGES)-mRNA levels. Contrasting with this is a decreased expression of PGF2alpha-synthase (PGFS/AKR1C3) in utero-placental compartments during prepartum luteolysis, suggesting an involvement of alternative synthetic pathways in PGF2alpha synthesis, e.g., conversion of PGE2 to PGF2alpha. However, since the expression and possible functions of the respective PTGES protein remained unknown, no further conclusion could be drawn. Therefore, a canine-specific PTGES antibody was generated and used to investigate the expression, cellular localization and biochemical activities of canine utero-placental PTGES throughout pregnancy and at prepartum luteolysis. Additionally, the biochemical activities of these tissues involved in the conversion of PGE2 to PGF2alpha were investigated. The endometrial PTGES was localized in the uterine surface epithelium pre-implantation, and in superficial and deep uterine glands, endothelial cells and myometrium throughout pregnancy and at parturition. Placental signals were mostly in the trophoblast. The biochemical properties of recombinant PTGES protein were confirmed. Additionally, expression of two PGE2-receptors, PTGER2/EP2 and PTGER4/EP4, revealed their decreasing expression during luteolysis. In contrast, the utero-placental expression of prostaglandin transporter (PGT) was strongly elevated prior to parturition. These localization patterns resembled that of PTGES. The increased expression of PTGES and PGT at parturition, together with the accompanying decreased levels of PGE2-receptors, and the capability of canine uterine and placental homogenates to take part in the conversion of PGE2 to PGF2alpha, as found in this study, suggest that PGE2 could be utilized locally as a substrate for prepartum PGF2alpha synthesis in the dog.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Veterinary Anatomy
Dewey Decimal Classification:570 Life sciences; biology
Date:8 October 2014
Deposited On:30 Oct 2014 16:02
Last Modified:05 Apr 2016 18:27
Publisher:Society for the Study of Reproduction
ISSN:0006-3363
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1095/biolreprod.114.122929
PubMed ID:25297547

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