NMR-based metabonomics for understanding the influence of dormant female genital tuberculosis on metabolism of the human endometrium

Subramani, Elavarasan; Jothiramajayam, Manivannan; Dutta, Mainak; Chakravorty, Debangana; Srivastava, Sudha; Mukherjee, Anita; Ray, Chaitali Datta; Chakravarty, B.N.; Chaudhury, Koel

doi:10.1093/humrep/dew003

Cited by 26 publications

(27 citation statements)

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“…Our earlier study on endometrial tissue NMR metabonomics revealed 21 significantly dysregulated metabolites in women with dormant GTB as compared to controls (Subramani et al 2016a). Interestingly, majority of the metabolites expressed in serum in the present study follow a similar trend as the expression observed in the endometrium of these women.…”

Section: Discussionsupporting

confidence: 78%

“…Levels of L-lysine, lactate, citrate, L-glutamine, L-histidine, L-threonine, L-phenylalanine, and L-tyrosine were found be increased in RSM cases compared to proven fertile women (Supplementary Table 2). The significantly altered metabolites discriminating dormant GTB and RSM cases are presented in Supplementary Table 2. In the present study, we have used Pearson's correlation analysis to identify the association of altered serum metabolites with dysregulated endometrial tissue metabolites in dormant GTB women, reported earlier (Subramani et al 2016a). This analysis shows significant positive correlation among serum metabolites (Fig.…”

Section: Resultsmentioning

confidence: 94%

“…We found that the energy metabolism and amino acid biosynthesis related metabolites were altered in dormant GTB women during the implantation window implicating their association with implantation failure (Subramani et al 2016a). We hypothesize that clinically relevant metabolites which can effectively discriminate between women with and without dormant GTB may be found in systemic circulation.…”

Section: Introductionmentioning

confidence: 82%

“…Recently, we used proton NMR metabonomics to study the metabolic influence of tuberculosis on the endometrium of women with dormant GTB (Subramani et al 2016a). We found that the energy metabolism and amino acid biosynthesis related metabolites were altered in dormant GTB women during the implantation window implicating their association with implantation failure (Subramani et al 2016a).…”

Section: Introductionmentioning

confidence: 99%

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Identification of serum metabolic markers for diagnosis of women with dormant genital tuberculosis

et al. 2016

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Introduction Genital tuberculosis (GTB) in women is one of the common causes of infertility in emerging countries. As an intracellular pathogen, Mycobacterium tuberculosis in the endometrium significantly alters the host metabolism in dormant GTB cases. Nuclear magnetic resonance (NMR) based metabolic profiling has emerged as a useful tool for identification of biomarkers in biological fluids. Objective To investigate NMR based serum metabolic profile of dormant GTB women as compared to controls. Methods Dormant GTB women (n = 26) and unexplained infertile women (controls; n = 26), healthy proven fertile women undergoing voluntary sterilization (n = 25) and women undergoing recurrent spontaneous miscarriage (RSM) (n = 27) were included in the study. 700 MHz proton NMR spectra of serum collected from these patients were recorded. Multivariate analysis including principal component analysis, partial least squares discriminant analysis and orthogonal projection to latent structurediscriminant analysis was applied to all the spectra. Association of dysregulated serum metabolites with our earlier findings related to altered endometrial tissue metabolites in dormant GTB women was studied using multiple correlation analysis. Results This study indicates a clear metabolic differentiation between women with dormant GTB and controls. Metabolites including 3-hydroxybutyrate, succinate, citrate, acetate, L-glutamine, L-lysine, glutamate, L-threonine and 1-methyl histidine were found to be significantly upregulated in serum of women with dormant GTB compared with controls. Pearson's correlation analysis showed a significant correlation between the expression of endometrial tissue and serum metabolites. Conclusions The set of identified metabolites may be considered as candidate markers for the diagnosis of dormant GTB and help clinicians in early therapeutic management.

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Section: Discussionsupporting

confidence: 78%

Section: Resultsmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

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Identification of serum metabolic markers for diagnosis of women with dormant genital tuberculosis

et al. 2016

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“…Proton nuclear magnetic resonance spectroscopy (1H NMR) is being commonly used for the quantitative assessment of low molecular weight metabolites and functional read-out of cellular phenotypic responses to disease and/or any chemical treatment 14, 16 . In an earlier study, we used 1H NMR metabonomics and could successfully characterize the metabolic profile of the endometrium obtained from women with GTB and healthy controls 17 . This study revealed the possible association of dysregulated energy metabolism and amino acid biosynthesis metabolites with repeated implantation failure in dormant GTB women 4 .…”

Section: Introductionmentioning

confidence: 99%

Mycobacterial heat shock protein 65 mediated metabolic shift in decidualization of human endometrial stromal cells

Subramani

Rameshbabu

Jothiramajayam

et al. 2017

Sci Rep

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Successful implantation is dependent on the appropriate decidualization of endometrial stromal cells for the establishment of pregnancy in women. Mycobacterial heat shock protein 65 (HSP65) is involved in pathogenesis of the genital tuberculosis (GTB), one of the common causes of infertility in emerging countries. Though implantation failure appears to be the major cause, understanding the status of decidualizaiton process in women diagnosed with GTB has not been thoroughly addressed. We, therefore, explored the effect of HSP65 protein on the endometrial cell metabolism during in vitro decidualization. In order to identify the cellular metabolism of decidual cells with and without HSP65 treatment, proton NMR based characterization of metabolites extracted from cells and culture media were performed. In presence of HSP65, significant reduction in the decidual phenotype of endometrial stromal cells and prolactin expression is suggestive of impairment in decidualization. The intracellular and extracellular metabolic changes in HSP65 treated endometrial stromal cells produced a distinct pattern, reflecting the interaction between the protein and cellular metabolism. HSP65 mediated dysregulation in cellular metabolism is associated with poor decidualization. Besides enriching the present knowledge on metabolic changes underlying stromal cells decidualization, these findings assist in identifying potential molecular causes for decidualization failure in GTB women.

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Creatine metabolism in the uterus: potential implications for reproductive biology

et al. 2020

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NMR-based metabonomics for understanding the influence of dormant female genital tuberculosis on metabolism of the human endometrium

Abstract: Government of India, Indian Council of Medical Research. There are no conflicts of interest.

Cited by 26 publications

References 55 publications

Identification of serum metabolic markers for diagnosis of women with dormant genital tuberculosis

Identification of serum metabolic markers for diagnosis of women with dormant genital tuberculosis

Mycobacterial heat shock protein 65 mediated metabolic shift in decidualization of human endometrial stromal cells

Creatine metabolism in the uterus: potential implications for reproductive biology

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