Molecular and morphological changes in placenta and embryo development associated to the inhibition
June 29th, 2008 | by admin |Molecular and morphological changes in placenta and embryo development associated to the inhibition of polyamine synthesis during midpregnancy in mice.
Polyamines play an essential role in murine development, as demonstrated by both gene ablation in ornithine decarboxylase (ODC)-deficient embryos and pharmacological treatments of pregnant mice. However, the molecular and cellular mechanisms by which ODC inhibition affects embryonic development during critical periods of pregnancy are mostly unknown. Our present results demonstrate that the contragestational effect of alpha-difluoromethylornithine (DFMO), a suicide inhibitor of ODC, when given at days 7-9 of pregnancy, is associated with embryo growth arrest and marked alterations in the development of yolk sac and placenta. Blood island formation was markedly decreased in the yolk sac, as well as the transcript levels of embryonary globins Hbax and Hbby. At the placental level, abnormal chorioallantoic attachment, absence of the spongiotrophoblast layer and a deficient development of the labyrinthine zone were evident. Real time RT-PCR analysis showed that transcript levels of the steroidogenic genes StAR, 3beta-hydroxysteroid dehydrogenase VI and 17alpha-hydroxylase were markedly decreased by DFMO treatment in the developing placenta at days 9 and 10 of pregnancy. Plasma values of progesterone and androstenedione were also decreased by DFMO treatment. Transcriptomic analysis also detected changes in the expression of several genes involved in placentation and in the differentiation of trophoblastic lineages. In conclusion, our results indicate that ODC inhibition at day 8 of pregnancy is related to alterations in yolk sac formation and trophoblast differentiation, affecting processes such as vasculogenesis and steroidogenesis.
López-GarcÃa C, López-Contreras AJ, Cremades A, Castells MT, MarÃn F, Schreiber F, Peñafiel R.
Departments of Biochemistry and Molecular Biology B and Immunology (CLG, AJLC, RP), Pharmacology (AC), Cell Biology (MTC), Human Anatomy, and Psicobiology (FM), Faculty of Medicine, University of Murcia, Spain; Team 15, Microbial Pathogenesis, Wellcome Trust Sanger Institute, Cambridge, UK (FS).