Complications in pregnancy
Why we work
We are studying different types of pregnancy complications, resulting in disturbed embryo-fetal development, mainly as a consequence of altered maternal metabolism (caused by diabetes, obesity, or ethanol intake).
We work with animal models in vivo, and in vitro culture of whole embryos, embryonic tissues and embryonic cells.
Our short-term aims are to clarify and understand the mechanisms and patterns of dysmorphogenesis; the long-term goal is to prevent the maternal and fetal damage.
Diabetes is a teratogen
Diabetes in the pregnant women is associated with an increased risk for malformations in the offspring and preeclampsia in the mother. We have studied the mechanisms behind the disturbed development of the offspring in animal models, embryo culture, as well as by in vitro culture of embryonic tissues and cells. We reported previously the occurrence of prostaglandin deficiency, inositol deficiency, as well as oxidative stress in embryos exposed to a diabetic environment. We have subsequently been able to diminish the diabetes-induced damages in the offspring by supplementing several agents to the pregnant mother or cultured embryo, such as arachidonic acid, inositol, or antioxidative compounds (N-acetylcysteine, BHT, vitamin E (tocopherol), vitamin C (ascorbic acid), folic acid, and ROS-scavenging enzymes).
We are currently investigating the importance of genetic predisposition for the development of malformations, a project, which is currently yielding data regarding the importance of the maternal and fetal genomes and epigenomes for the development of fetal dysmorphogenesis in diabetic pregnancy.
We have identified one gene, Gpx-1, which is underexpressed in malformed offspring of diabetic rats (compared with non-malformed offspring of same litter), and its gene product, the antioxidative enzyme Glutathione Peroxidase-1, is less distributed in the embryonic tissues, and its enzymatic activity markedly decreased. These findings can be related to the enhanced oxidative stress involved in the embryo-fetal dysmorphogenesis of diabetic pregnancy.
We have created and studied an animal model of preeclampsia (with and without maternal diabetes) and attempted to diminish the negative consequences of the complication by maternal treatment with large doses of antioxidants.
Obesity is a teratogen
Obesity in the pregnant woman is associated with increased risk for congenital malformations, in particular the risk for neural tube defects and cardiac malformations been found to be increased. We are currently involved in creating an animal model for this type of pregnancy, as well as attempting to affect embryonic development in vitro by subjecting the embryos and embryonic cells to fatty acids and other lipid compounds.
We are presently studying maternal metabolic state and fetal outcome in rats fed a lipid-enriched diet (O) from weaning to adulthood and throughout pregnancy and comparing the fetal outcome with that of control rats (C) on a regular diet. We make the comparisons on gestational day 10 and 11 as well as on gestational day 20 with regard to neural tube defects, oxidative stress and inflammation-related gene expression. In addition, we will also investigate the impact of serum collected from O pregnant rats on C embryonic development in whole embryo culture.
Alcohol is a teratogen
Intake of ethanol during pregnancy can seriously harm the offspring; the risk increases with increased exposure. We have studied this situation, and attempted to alter the fetal defense against free oxygen radicals in vivo and in vitro, in order to diminish the ethanol-induced damage. We are studying possible biomarkers for maternal ethanol intake, by investigating embryonic tissues exposed to ethanol.
We are currently conducting a collaborative study on the dietary habits during pregnancy of women who have given birth to a child with Attention-Deficit/Hyperactivity Disorder.
What we hope
The teratogens we are studying are structurally different, but their destructive damages are similar. We hope to find one or several common keys to the understanding of their effects.