title: Dysregulated leukemia inhibitory factor and its receptor regulated signal transducers and activators of transcription 3 pathway: a possible cause for repeated implantation failure in women with dormant genital tuberculosis?
abstract: OBJECTIVE
  To investigate the influence of dormant Mycobacterium tuberculosis on the expression of various endometrial receptivity markers and leukemia inhibitory factor (LIF)-signal transducers and activators of transcription 3 (STAT3) signaling pathway. Expression of endometrial receptivity markers and LIF-STAT3 signaling in in vitro decidualized human endometrial stromal cells (hESC) treated with 65 kDa mycobacterial heat shock protein (HSP65) is also explored.
  
  
  METHODS
  A prospective study.
  
  
  METHODS
  Tertiary care hospital and reproductive health research unit.
  
  
  METHODS
  Endometrial tissue samples were collected from 38 women who tested positive for Mycobacterium tuberculosis and 30 normal women with proven fertility undergoing sterilization. In vitro decidualization of hESC was performed.
  
  
  METHODS
  Endometrial biopsies collected from all women during implantation window and treatment of hESC with HSP65.
  
  
  METHODS
  Measurement of various endometrial receptivity markers including αvβ3 integrin, E-cadherin, MECA-79, mucin-1, and pinopodes and LIF/LIFR-STAT3 signaling molecules expressed in the endometrium of women with dormant genital tuberculosis (GTB) during implantation window and measured also in HSP65-treated hESC.
  
  
  RESULTS
  Significantly reduced levels of endometrial receptivity markers LIF, LIFR, and pSTAT3 were observed in endometrium of women with dormant GTB as compared with controls. A similar trend was observed under in vitro conditions with decreased level of phosphorylated STAT3 in HSP65-treated hESC. However, no change in the expression of endometrial receptivity markers under in vitro conditions was observed.
  
  
  CONCLUSIONS
  Our findings suggest that endometrium of women with dormant GTB is associated with poor receptivity, as evidenced by reduced receptivity markers and aberrant LIF-STAT3 signaling. In vitro treatment of hESC with HSP65 also confirms compromised endometrial decidualization.
authors.affiliation: School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, India; Department of Animal Science, McGill University, Ste-Anne-de-Bellevue, Quebec, Canada.
authors.forename: Elavarasan
authors.initials: E
authors.lastname: Subramani
authors.affiliation: Department of Animal Science, McGill University, Ste-Anne-de-Bellevue, Quebec, Canada.
authors.forename: Ejimedo
authors.initials: E
authors.lastname: Madogwe
authors.affiliation: Department of Gynaecology and Obstetrics, Institute of Post-Graduate Medical Education and Research and SSKM Hospital, Kolkata, India.
authors.forename: Chaitali Datta
authors.initials: CD
authors.lastname: Ray
authors.affiliation: Department of Pathology, Scientific Clinical Research Laboratory, Kolkata, India.
authors.forename: Subir Kumar
authors.initials: SK
authors.lastname: Dutta
authors.affiliation: Institute of Reproductive Medicine, Salt Lake, Kolkata, India.
authors.forename: Baidyanath
authors.initials: B
authors.lastname: Chakravarty
authors.affiliation: Department of Animal Science, McGill University, Ste-Anne-de-Bellevue, Quebec, Canada.
authors.forename: Vilceu
authors.initials: V
authors.lastname: Bordignon
authors.affiliation: Department of Animal Science, McGill University, Ste-Anne-de-Bellevue, Quebec, Canada.
authors.forename: Raj
authors.initials: R
authors.lastname: Duggavathi
authors.affiliation: School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, India. Electronic address: koel@smst.iitkgp.ernet.in.
authors.forename: Koel
authors.initials: K
authors.lastname: Chaudhury
mesh_terms: D000328:Adult; D002461:Cell Line, Transformed; D010064:Embryo Implantation / Q000502:physiology*; D004717:Endometrium / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007247:Infertility, Female / Q000175:diagnosis / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor / Q000378:metabolism*; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit / Q000378:metabolism*; D011446:Prospective Studies; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D014384:Tuberculosis, Female Genital / Q000175:diagnosis / Q000378:metabolism*
chemical_list: C507837:LIF protein, human; C507840:LIFR protein, human; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: Endometrial receptivity; HSP65; decidualization; dormant genital tuberculosis; infertility