Specific clinical biomarkers have the potential to revolutionize diagnosis and treatment of various medical conditions, ranging from abnormal pregnancies to myocardial infarctions and cancer. In particular, a theme of current cancer research is the quest for sensitive biomarkers that can be exploited to detect early neoplastic changes. Ideally, biomarkers should be easily accessible such that they can be sampled non-invasively. Therefore biomarkers that can be sampled from body fluids, such as serum or urine, are particularly desirable. In recent years it has become clear that both cell-free DNA and mRNA are present in serum, as well as in other body fluids, and that these CNAs represent potential biomarkers 
. Accordingly, we considered it likely that microRNAs might be present in bodily fluids.
MicroRNAs are a recently discovered class of small non-coding RNAs that regulate gene expression and have a critical role in many biological and pathological processes 
. In general, microRNAs are regulated and transcribed like protein coding genes. Subsequent microRNA biogenesis involves discrete processing and transport steps, whereby the active moiety of 20–22 nucleotides is excised from a longer RNA precursor that exhibits specific hairpin structure. Finally, these 20–22 nucleotides are incorporated into a composite machinery, which promotes partial duplex formation between the short RNA and the 3′ untranslated regions (UTR) of targeted mRNAs, resulting typically in mammals in translational silencing 
. A relevant, though at present enigmatic, feature of microRNA biology is their remarkable stability. For example, microRNAs are preserved well in tissue samples even after formalin-fixation and paraffin-embedding and can be efficiently extracted and evaluated 
. Therefore, if microRNAs are indeed circulating, we hypothesized further that they should preserve their stability in body fluids. Monitoring the typically small amounts of CNAs in body fluids requires complex and sensitive extraction and detection methods, which until now have been prohibitive either practically or economically 
. However, we anticipated that the stability of microRNAs should allow development of practicable detection methods, such that they can realistically serve as clinical biomarkers.
Although the total number of microRNAs remains controversial 
and the roles of specific microRNAs are only beginning to be defined, microRNA expression analyses indicate that diverse tumors display microRNA expression profiles (for mature and/or precursor microRNAs) significantly different from normal tissue 
. Furthermore, microRNAs are emerging as highly tissue-specific biomarkers 
with potential clinical applicability for defining the cancer origin of metastases, as we have shown recently 
. These data led us to expect that the microRNA abundance profile of bodily fluids might reflect physiological and/or pathological conditions and, furthermore, might do so more accurately than an mRNA abundance profile. For mRNA must be translated into protein to have a biological effect whereas microRNAs are themselves the active moiety, often influencing the expression of multiple other genes, and thus likely reflect altered physiology more directly.
Here we validate that microRNAs are present in body fluids and moreover, demonstrate that microRNA levels in serum reflect altered physiological conditions, such as pregnancy.