Purpose: Early pregnancy loss (EPL) is one of the most common complications encountered in clinical practice. As most of EPLs occur relatively early on during pregnancy, they are often misunderstood as an expected menstrual cycle. Thus, it is essential to investigate the diagnostic biomarkers for monitoring pregnancy loss for continuous non-invasive monitoring of EPL.
Experimental design: Unstimulated saliva was collected from 10 subjects with EPL and a matched cohort of healthy pregnant women as controls. Samples were analyzed using iTRAQ analysis, and ELISA was performed to validate results.
Results: Enrichment analysis of the 38 differentially abundant proteins identified that regulation of nucleobase, nucleoside, nucleotide, and nucleic acid metabolism was significantly affected in EPL. The nucleosome assembly pathway was significantly underrepresented in EPL and was associated with depletion of histone proteins (H2B, H3, and H4). These results were validated with ELISA experiments. A depletion of histones can impair nucleosome assembly and cause the nuclear machinery to fail.
Conclusion: Regulation of nucleosome is critical for the maintenance of genome stability and epigenetic information, lack of which may lead to pregnancy loss. Thus, assessing and monitoring salivary histone levels in patients with threatened miscarriage can be a quick and easy method of obtaining periodic diagnostic information that can speed up treatment decisions.
Clinical relevance: There is considerable uncertainty regarding the prognosis of threatened pregnancy, making it stressful for expecting mothers and healthcare professionals. Most EPLs are often misunderstood or ignored as an expected menstrual cycle. Thus it is essential to develop screenings and rapid detection devices using a medium that can be non-invasive and self-performed for continuous monitoring. Using saliva, we have identified that the nucleosome assembly gets affected in EPL with depletion of histone proteins (H2B, H3, and H4). With further verification, these findings can help saliva be utilized as a medium to determine which patients will/will not progress to miscarriage and at what point of their pregnancy. Assessing and monitoring EPL using salivary diagnostics can be a quick and easy method of obtaining periodic diagnostic information that can speed up treatment decisions. Hence, these findings need to be investigated further to improve the prediction of outcomes in women with threatened pregnancy.
Keywords: early pregnancy loss; miscarriage; proteomics; saliva.
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