Abstract
BackgroundValproate, thalidomide and alcohol (ethanol) exposure during the first trimester of pregnancy is known to cause several developmental disorders. All these teratogens are known to pass the placental barrier and interfere directly with the normal development of the fetus. However, these teratogens also alter the formation and function of the placenta itself which may in turn affect the proper nourishment and development of the fetus. Optimum development of the placenta requires adequate invasion of trophoblast into the maternal uterine tissues. Changes in the migratory behavior of trophoblast by maternal exposure to these teratogens during placentogenesis may therefore alter the structure and function of the placenta.MethodsIn the present study, the effects of sodium valproate, thalidomide and alcohol on the migration of human first trimester trophoblast cell line (HTR-8/SVneo) were examined in vitro. Cells were cultured in the wells of 48-well culture plates as mono or multilayers. Circular patches of cells were removed from the center of the wells by suction, and the migration of cells into the wound was studied using microscopy. Effects of low and high concentrations of valproate, thalidomide and alcohol were examined on the healing of wounds and on the migration rate of cells by determining the wound areas at 0, 3, 6, 12, 24 and 48 h. Effects of drugs and alcohol on the proliferation and the expression levels of integrin subunits beta1 and alpha5 in cells were examined.ResultsThe migration rates of trophoblast differed between wounds created in mono and multilayers of cells. Exposure to teratogens altered the migration of trophoblast into mono and multilayer wounds. The effects of valproate, thalidomide and alcohol on the proliferation of cells during the rapid migratory phase were mild. Drug exposure caused significant changes in the expression levels of beta1 and alpha5 integrin subunits.ConclusionResults suggest that exposure to valproate, thalidomide or alcohol during the first trimester of pregnancy may change the ultrastructure of the placenta by altering the migration of trophoblast cells and this effect may be mediated by drug- or alcohol-induced changes in the expression levels of beta1 and alpha5 integrin subunits.
Highlights
Valproate, thalidomide and alcohol exposure during the first trimester of pregnancy is known to cause several developmental disorders
The results suggest that valproate, thalidomide and alcohol may influence migration of human first trimester trophoblast
Results demonstrate that the changes in the migration rate of human first trimester trophoblast after drug and alcohol treatments may result from the alteration in the expression levels of β1 and α5 integrin subunits
Summary
Thalidomide and alcohol (ethanol) exposure during the first trimester of pregnancy is known to cause several developmental disorders All these teratogens are known to pass the placental barrier and interfere directly with the normal development of the fetus. The immunomodulatory and anticancer drug thalidomide (THA) passes through the placental barrier and causes several defects in children including neurobehavioral problems, ear and limb malformations [12]. Use of this drug during pregnancy is prohibited in the United States, it remains a potential teratogen in many parts of the world [13,14,15]. It is possible that these teratogens may alter the number and the invasion of trophoblasts, changing placental ultrastructure
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