CYP26A1-specific antagonist influence on embryonic implantation, gene expression and endogenous retinoid concentration in rats.
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.
Fritzsche
Britta
B
Institute of Nutritional Science, Department of Physiology and Pathophysiology of Nutrition, University of Potsdam, Nuthetal, Germany. britta.fritzsche@gmail.com
Schuchardt
Jan-Philipp
JP
Schmidt
Anja
A
Nau
Heinz
H
Schweigert
Florian J
FJ
Rühl
Ralph
R
D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D010064:Embryo Implantation / Q000187:drug effects* / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D000072516:Retinoic Acid 4-Hydroxylase; D012176:Retinoids / Q000097:blood* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014230:Triazoles / Q000494:pharmacology*; D014599:Uterus / Q000201:enzymology / Q000378:metabolism
D052160:Benzothiazoles; D065607:Cytochrome P-450 Enzyme Inhibitors; D012176:Retinoids; D014230:Triazoles; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase; C406527:R 115866