The possibility that miRs might modulate mRNA levels and subsequent toxicity by TCDD has not been fully explored. Recently, a few studies have begun exploring such mechanisms. One study reported that miR-27b related to AhR-regulated genes increased CYP1B1 levels. In another study, it was noted that treatment with TCDD in vivo caused few changes in miR levels in mouse or rat livers, and those changes that were statistically significant were of modest magnitude. These data are consistent with our studies where we noted that the magnitude of change in miR expression following TCDD treatment in most Tulathromycin B instances was 1.5 to 2 fold and only a few miRs showed 3�C8 fold change. The fact that liver may be more refractory was also indicated in another study in which it was noted that AhR activation by benzopyrene did not cause significant changes in miRs of the liver but altered the miR profiles in the lung. The miRs that were altered by BaP were involved in immune response, cell proliferation and cell cycle. Thus, it is likely that the AhR-agonist mediated changes in miRs may be organ-specific. While, the immunotoxic effects of prenatal exposure to TCDD on fetal thymocytes have been well characterized, there are no reports on such effects of TCDD on miR profiles. Understanding the role of various miRs in neonatal mice post-TCDD exposure may shed light on the “fetal basis of adult disease” hypothesis. This hypothesis proposes that many chronic diseases including autoimmune diseases during adult stage of life may be the result of prenatal exposure to nutritional, environmental or other forms of stress. In this study, therefore, we sought to examine miR profile in fetuses post-TCDD exposure. The cluster analysis data of miRs showed that TCDD caused significant changes in miR expression profile in fetal thymi when compared to vehicle-treated thymi. Of the miRs screened, 78 miRs were altered more than 1.5 fold and 28 miRs were altered two fold or more, post-TCDD exposure. We further validated the expression profile of some select miRs by performing Real-Time PCR. All the miRs that we analyzed by Real-Time PCR corroborated the data obtained from miR array analysis. Furthermore, the relationship of miRs and their target gene expression was also verified. For example, miRs that showed highly complementary sequence with 39UTR of AhR, CYP1A1, Fas, and FasL genes were downregulated by TCDD in fetal thymi and the data obtained from RT-PCR showed upregulated expression of the above genes in fetal thymi post-TCDD exposure. such as breast, cartilage, endothelial cells, embryonic tissues, etc. These downregulated miRs have been shown to control genes that are involved in various physiological functions in these tissues. Previous studies from our laboratory have demonstrated that TCDD-induced thymic atrophy in the adult and fetus may result, at least in part, from induction of apoptosis. We have also reported that such Folinic acid calcium salt pentahydrate apoptosis may be induced through the extrinsic pathway by the induction of Fas and FasL in thymocytes. Also miR200a has been shown to regulate apoptosis, whereas miR-491 has been shown to induce apoptosis by targeting Bcl-xL gene. Thus, these miRs may directly/indirectly be involved in apoptosis of thymic 
cells leading to thymic atrophy. TCDD has also been shown to cause cancer in various species and it is also considered to be a potential carcinogen in humans. There are reports demonstrating that TCDD exposure of mice triggers cutaneous papillomas and squamous cell carcinoma. In another report, prenatal TCDD exposure of rats was shown to make them susceptible to breast cancer. TCDD has also been shown to promote liver cancer. miRs have been shown to influence signaling pathways leading to development of various types of cancer.