Teratogen-induced alterations in microRNA-34, microRNA-125b and microRNA-155 expression: correlation with embryonic p53 genotype and limb phenotype.

Background: In a large number of studies, members of the microRNA (miRNA)-34 family such as miRNA-34a, miRNA-34b, miRNA-34c, as well as miRNA-125b and miRNA-155, have been shown to be regulators of apoptosis. The ability of these miRNAs to perform this function is mainly attributed to their ability to interact with the p53 tumor suppressor, which is a powerful regulator of the teratologic susceptibility of embryos. We chose to explore whether miRNA-34a/b/c, miRNA-125b and miRNA-155 may play a role in teratogenesis by using p53+/- pregnant mice treated with cyclophosphamide (CP) as a model.

Teratogen-induced distortions in the classical NF-kappaB activation pathway: correlation with the ability of embryos to survive teratogenic stress.

Studies with diverse teratogens implicated the transcription factor NF-kappaB in mechanisms determining teratological susceptibility of embryos. Here, a teratogen such as cyclophosphamide (CP) was used to test whether teratogenic insult alters the classical NF-kappaB activation pathway, and how these alterations correlate with the ability of mouse embryos to resist the teratogen-induced process of maldevelopment. We observed that embryos tested 24 h after the exposure of females to 40 mg/kg CP exhibited a dramatic decrease in the level of NF-kappaB (p65 subunit)-DNA binding, IkappaB kinase beta (IKKbeta) activity, expression of p65 and IKKbeta proteins, as well as NF-kappaB inhibitory proteins (IkappaBs) such as IkappaBalpha, IkappaBbeta, and IkappaBepsilon, and died within the next 24 h.