1H-NMR based metabolomic profiling of cord blood in gestational hypothyroidism

Abstract

Background: Gestational hypothyroidism (GHT) is a common pregnancy-related thyroid disfunction.The adverse outcomes by GHT has been increasingly recognized, leading to more public awareness of the disease. However, comprehensive understanding of the prognosis of GHT has not yet achieved.Metabolomics is a powerful tool in evaluation of disease outcomes, and cord blood represents an excellent candidate for the investigation of gestational outcomes. Methods:In the present study, we performed 1H-NMR based metabolomics on cord blood of 18 pregnant women with GHT and 18 non hypothyroidism (NHT) control. Results:The metabolomic profile of GHT was separated with the NHT control. A total of 8 metabolites with altered abundances were observed, among which Creatinine and O-Phosphocholine were elevated and the others were downregulated in GHT. Spearman rank correlation suggested that the eight differential metabolites were correlated with the GHT related thyroid hormones. Pathway analysis of the differential metabolites indicated that two metabolic pathways were significantly altered in GHT (adjusted P<0.05), including tyrosine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis. Enrichment analysis of the differential metabolites against disease-associated metabolite sets suggested that GHT was associated with disease risks of non-insulin dependent diabetes mellitus, isovaleric acidemia, and methylmalonic aciduria. Conclusions:The results of this study revealed GHT associated metabolic changes in cord blood, providing insights into the metabolic intermediates between GHT and its related disease risks.

Cord blood metabolomics reveals gestational metabolic disorder associated with anti-thyroid peroxidase antibodies positivity

“…Accordingly, amino acid metabolism pathways were reported to be potential drug targets in autoimmune diseases [ 48 ], and played an important role in immune responses by regulating T/B lymphocytes, cellular redox state, and antibodies production [ 49 ]. Several metabolic pathways observed in the present study were reported to be significantly altered in hypothyroidism, including the down-regulation of nicotinate and nicotinamide metabolism in hypothyroidism rats [ 50 ], the increased activity of urea cycle in animal models of hypothyroidism [ 51 ], the significantly altered phenylalanine, tyrosine and tryptophan biosynthesis in GH [ 28 ], the significantly increased phenylalanine metabolism in a hypothyroidism model [ 52 ]. While increased activity of the glucose-alanine cycle was beneficial in the control of glucose utilization without increasing the risk of hypoglycemia in hyperthyroidism [ 53 ], thyroid hormone enhanced the Warburg Effect in breast cancer [ 54 ].…”

“…Cord blood sample preparation for 1H-NMR spectral profiling was performed according to a previously reported procedure [ 28 ]. Briefly, a volume of 450 μl sample was mixed with 900 μl methanol (HPLC grade), vortexed for 5 min and then centrifuged at 4℃, 15, 000 rpm for 20 min for protein precipitation.…”