CYP26A1-specific antagonist influence on embryonic implantation, gene expression and endogenous retinoid concentration in rats

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Autoren

Externe Organisationen

  • Universität Potsdam
  • Bayer Pharma AG
  • Stiftung Tierärztliche Hochschule Hannover
  • University of Debrecen
  • Forschungsgruppe Apoptose und Genomik der Ungarischen Akademie der Wissenschaften, Debrecen
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Details

OriginalspracheEnglisch
Seiten (von - bis)446-451
Seitenumfang6
FachzeitschriftReproductive Toxicology
Jahrgang30
Ausgabenummer3
PublikationsstatusVeröffentlicht - Nov. 2010

Abstract

Retinoids are essential in vertebrate reproduction and embryonic development. All-trans-retinoic acid (ATRA) is tightly regulated during these processes. CYP26A1 is mainly responsible for its degradation. To study the role of CYP26A1 during implantation, we applied R115866, a CYP26A1-specific antagonist, to rats during early gestation days (GD). On GD 6.5 and 12 samples were collected and the number of embryos was evaluated. ATRA concentration increased in uterus and serum, mRNA expression of CYP26A1 and CRABP2 increased in the liver, but not in the uterus. Uterine COX1 and 17βHSD mRNA expression was decreased. The number of embryos on GD 12 was not altered in this setting. It can be concluded that uterine expression of the analyzed retinoid-response genes during early gestation is not altered by this R115866 treatment and instead indirectly via ATRA. From our experiment we cannot confirm that ATRA obtains a major influencing role in the regulation of embryonic implantation.

Zitieren

CYP26A1-specific antagonist influence on embryonic implantation, gene expression and endogenous retinoid concentration in rats. / Fritzsche, Britta; Schuchardt, Jan Philipp; Schmidt, Anja et al.
in: Reproductive Toxicology, Jahrgang 30, Nr. 3, 11.2010, S. 446-451.

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Fritzsche B, Schuchardt JP, Schmidt A, Nau H, Schweigert FJ, Rühl R. CYP26A1-specific antagonist influence on embryonic implantation, gene expression and endogenous retinoid concentration in rats. Reproductive Toxicology. 2010 Nov;30(3):446-451. doi: 10.1016/j.reprotox.2010.05.005
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title = "CYP26A1-specific antagonist influence on embryonic implantation, gene expression and endogenous retinoid concentration in rats",
abstract = "Retinoids are essential in vertebrate reproduction and embryonic development. All-trans-retinoic acid (ATRA) is tightly regulated during these processes. CYP26A1 is mainly responsible for its degradation. To study the role of CYP26A1 during implantation, we applied R115866, a CYP26A1-specific antagonist, to rats during early gestation days (GD). On GD 6.5 and 12 samples were collected and the number of embryos was evaluated. ATRA concentration increased in uterus and serum, mRNA expression of CYP26A1 and CRABP2 increased in the liver, but not in the uterus. Uterine COX1 and 17βHSD mRNA expression was decreased. The number of embryos on GD 12 was not altered in this setting. It can be concluded that uterine expression of the analyzed retinoid-response genes during early gestation is not altered by this R115866 treatment and instead indirectly via ATRA. From our experiment we cannot confirm that ATRA obtains a major influencing role in the regulation of embryonic implantation.",
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author = "Britta Fritzsche and Schuchardt, {Jan Philipp} and Anja Schmidt and Heinz Nau and Schweigert, {Florian J} and Ralph R{\"u}hl",
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TY - JOUR

T1 - CYP26A1-specific antagonist influence on embryonic implantation, gene expression and endogenous retinoid concentration in rats

AU - Fritzsche, Britta

AU - Schuchardt, Jan Philipp

AU - Schmidt, Anja

AU - Nau, Heinz

AU - Schweigert, Florian J

AU - Rühl, Ralph

N1 - Copyright © 2010 Elsevier Inc. All rights reserved.

PY - 2010/11

Y1 - 2010/11

N2 - Retinoids are essential in vertebrate reproduction and embryonic development. All-trans-retinoic acid (ATRA) is tightly regulated during these processes. CYP26A1 is mainly responsible for its degradation. To study the role of CYP26A1 during implantation, we applied R115866, a CYP26A1-specific antagonist, to rats during early gestation days (GD). On GD 6.5 and 12 samples were collected and the number of embryos was evaluated. ATRA concentration increased in uterus and serum, mRNA expression of CYP26A1 and CRABP2 increased in the liver, but not in the uterus. Uterine COX1 and 17βHSD mRNA expression was decreased. The number of embryos on GD 12 was not altered in this setting. It can be concluded that uterine expression of the analyzed retinoid-response genes during early gestation is not altered by this R115866 treatment and instead indirectly via ATRA. From our experiment we cannot confirm that ATRA obtains a major influencing role in the regulation of embryonic implantation.

AB - Retinoids are essential in vertebrate reproduction and embryonic development. All-trans-retinoic acid (ATRA) is tightly regulated during these processes. CYP26A1 is mainly responsible for its degradation. To study the role of CYP26A1 during implantation, we applied R115866, a CYP26A1-specific antagonist, to rats during early gestation days (GD). On GD 6.5 and 12 samples were collected and the number of embryos was evaluated. ATRA concentration increased in uterus and serum, mRNA expression of CYP26A1 and CRABP2 increased in the liver, but not in the uterus. Uterine COX1 and 17βHSD mRNA expression was decreased. The number of embryos on GD 12 was not altered in this setting. It can be concluded that uterine expression of the analyzed retinoid-response genes during early gestation is not altered by this R115866 treatment and instead indirectly via ATRA. From our experiment we cannot confirm that ATRA obtains a major influencing role in the regulation of embryonic implantation.

KW - Animals

KW - Benzothiazoles/pharmacology

KW - Body Weight/drug effects

KW - Chromatography, High Pressure Liquid

KW - Cytochrome P-450 Enzyme Inhibitors

KW - Cytochrome P-450 Enzyme System

KW - Embryo Implantation/drug effects

KW - Female

KW - Gene Expression/drug effects

KW - Liver/enzymology

KW - Organ Size/drug effects

KW - Pregnancy

KW - Rats

KW - Rats, Wistar

KW - Retinoic Acid 4-Hydroxylase

KW - Retinoids/blood

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Triazoles/pharmacology

KW - Uterus/enzymology

U2 - 10.1016/j.reprotox.2010.05.005

DO - 10.1016/j.reprotox.2010.05.005

M3 - Article

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VL - 30

SP - 446

EP - 451

JO - Reproductive Toxicology

JF - Reproductive Toxicology

SN - 0890-6238

IS - 3

ER -

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