Protein signatures linking history of miscarriages and metabolic syndrome: a proteomic study among North Indian women

Abstract

BackgroundMetabolic syndrome (MeS), a constellation of metabolic adversities, and history of miscarriage make women at a higher risk for cardiovascular diseases (CVDs). However, molecular evidence indicating a link between the two phenotypes (history of miscarriage and MeS) among women would offer an opportunity to predict the risk factor for CVDs at an early stage. Thus, the present retrospective study attempts to identify the proteins signatures (if any) to understand the connection between the history of miscarriage and MeS.MethodsAge-matched 80 pre-menopausal women who were not on any medical intervention or drugs were recruited from a Mendelian population of the same gene pool. Recruited women were classified into four groups—(a) Group A—absolute cases with history of miscarriage and MeS, (b) Group B—absolute controls without any history of miscarriage and MeS, (c) Group C—cases with MeS but lack any history of miscarriage, (d) Group D—cases with history of miscarriage but lack MeS. Differentially expressed proteins in plasma samples of women from four groups were identified using 2-D gel electrophoresis and mass spectrometry.ResultsThree case groups (A, C, and D) showed 18 differentially expressed proteins. Nearly 60% of proteins (11/18) were commonly dysregulated in Group C (only with MeS) and Group D (only with miscarriage history). Nearly 40% of proteins (7/18) were commonly dysregulated in the three case groups (Groups A, C, and D), indicating a shared pathophysiology. Four proteins were exclusive but shared by case groups C and D indicating the independent routes for CVDs through MeS or miscarriages. In absolute cases, transthyretin (TTR) showed exclusive upregulation, which was further validated by Western blotting and ELISA. Networking analyses showed the strong association of TTR with haptoglobin, transferrin and ApoA1 hinting toward a cross-talk among these proteins which could be a cause or an effect of TTR upregulation.ConclusionThe study provides evidence for molecular link between the history of miscarriage and MeS through a putative role of TTR. However, longitudinal follow-up studies with larger sample size would further help to demonstrate the significance of TTR and other targeted proteins in risk stratification and the onset of CVDs.

Long term miscarriage-related hypertension and diabetes mellitus. Evidence from a United Kingdom population-based cohort study

“…A study by Smith et al noted that women with history of two or more pregnancy losses prior to their first delivery had higher risk of family history of coronary heart disease [17]. Women with history of miscarriage may have an underlying susceptibility to metabolic syndrome, a condition that manifests with a combination of high blood glucose, hypertension, obesity and dyslipidemia [39].…”

Recent Progress in Metabolic Syndrome Research and Therapeutics

“…To investigate the influence of protein signatures on cellular behavior, proteomic studies of visceral adipose tissue from metabolically unhealthy obese patients have illustrated that pathways related to cell migration, development of the hematological system, and immune cell trafficking can be drastically impacted [63]. For other comorbidities of MetS, transthyretin was identified as a molecular linkage between miscarriage and MetS [64]. The static status was assessed, the dynamics of proteomic evolvement carries clinical implications as well.…”