title: NMR-based metabonomics for understanding the influence of dormant female genital tuberculosis on metabolism of the human endometrium.
abstract: OBJECTIVE
  Does investigation of metabolic perturbations in endometrial tissue of women with dormant genital tuberculosis (GTB) during the window of implantation (WOI) assist in improving the understanding of endometrial receptivity?
  
  
  CONCLUSIONS
  In dormant GTB cases significant alterations in endometrial tissue metabolites occur, largely related to energy metabolism and amino acid biosynthesis in dormant GTB cases.
  
  
  BACKGROUND
  As an intracellular pathogen, Mycobacterium tuberculosis strongly influences the metabolism of host cells causing metabolic dysregulation. It is also accepted that dormant GTB impairs the receptive status of the endometrium. Global metabolic profiling is useful for an understanding of disease progression and distinguishing between diseased and non-diseased groups.
  
  
  METHODS
  Endometrial tissue samples were collected from patients reporting at the tertiary infertility care center during the period September 2011-March 2013. Women having tested positive for GTB were considered as the study group (n = 24). Normal healthy women undergoing sterilization (n = 26) and unexplained infertile women with repeated IVF failure (n = 21) volunteered to participate as controls.
  
  
  METHODS
  Endometrial tissue samples were collected 6-10 days after confirmation of ovulation. PCR and BACTEC-460 culture were used for diagnosing GTB. Proton nuclear magnetic resonance (1H NMR) spectra of tissue were recorded using a 700 MHz Bruker Avance AV III spectrometer. Following phase and baseline correction of all NMR spectra by Bruker Topspin 2.1 software, spectral peak alignment of the data was performed. Multivariate analysis was applied to all spectra and individual metabolites identified and multiple correlation analysis was performed.
  
  
  RESULTS
  Leucine, isoleucine, acetate, lactate, glutamate, glutamine, methionine, lysine, creatine, glycogen, glycine, proline and choline were found to be significantly increased (P < 0.05) in endometrial tissue of women with dormant GTB compared with unexplained infertile women with repeated implantation failure. Valine, citrate, succinate and aspartate were also observed to be significantly up-regulated (P < 0.01). Furthermore, a significant decrease in glucose (P < 0.05), threonine (P < 0.05), tyrosine (P < 0.01) and phenylalanine (P < 0.0001) was observed in women with dormant GTB. Pearson's correlation analysis between the expression of various endometrial receptivity markers and metabolites showed a significant negative correlation (-0.236 to -0.545, P < 0.05). Also, the metabolites were positively correlated with endometrial receptivity markers (0.207 to 0.618, P < 0.05).
  
  
  CONCLUSIONS
  It is often difficult to diagnose dormant GTB because it tends to exist without any clinical signs or symptoms. In addition, the diagnosis of GTB by culture remains a challenge due to low detection rates and its paucibacillary nature. Testing for prostate-specific antigen or the Y chromosome in order to account for the possible influences of recent exposure to semen on endometrial metabolism would be important.
  
  
  CONCLUSIONS
  The metabolic changes associated with the dormant tubercle infection are of potential relevance to clinicians for the treatment of dormant GTB-related infertility.
  
  
  BACKGROUND
  Government of India, Indian Council of Medical Research. There are no conflicts of interest.
authors: School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.
authors: E
authors: E
authors: Subramani
authors: Cell Biology and Genetic Toxicology Laboratory, Centre of Advanced study, Department of Botany, University of Calcutta, Kolkata 700019, India.
authors: M
authors: M
authors: Jothiramajayam
authors: School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.
authors: M
authors: M
authors: Dutta
authors: School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.
authors: D
authors: D
authors: Chakravorty
authors: National Facility for High-field NMR, Tata Institute of Fundamental Research, Mumbai 400005, India.
authors: M
authors: M
authors: Joshi
authors: National Facility for High-field NMR, Tata Institute of Fundamental Research, Mumbai 400005, India.
authors: S
authors: S
authors: Srivastava
authors: Cell Biology and Genetic Toxicology Laboratory, Centre of Advanced study, Department of Botany, University of Calcutta, Kolkata 700019, India.
authors: A
authors: A
authors: Mukherjee
authors: Department of Obstetrics and Gynaecology, Institute of Post-Graduate Medical Education and Research (IPGME&R) and SSKM Hospital, Kolkata 700020, India.
authors: C
authors: C
authors: Datta Ray
authors: Institute of Reproductive Medicine, Kolkata 700020, India.
authors: B N
authors: BN
authors: Chakravarty
authors: School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India koel@smst.iitkgp.ernet.in koeliitkgp@gmail.com.
authors: K
authors: K
authors: Chaudhury
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000096:biosynthesis; D058345:Asymptomatic Infections; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D004717:Endometrium / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D004734:Energy Metabolism; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D007194:India; D007247:Infertility, Female / Q000209:etiology; D055432:Metabolomics / Q000379:methods*; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification / Q000502:physiology*; D019906:Nuclear Magnetic Resonance, Biomolecular; D062606:Tertiary Care Centers; D014384:Tuberculosis, Female Genital / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology
chemical_list: D000596:Amino Acids; D015415:Biomarkers
keywords: dormant genital tuberculosis; endometrial receptivity; endometrial tissue; metabonomics; proton nuclear magnetic resonance