title: Preterm delivery and associated negative pregnancy outcome - A tale of faulty progesterone receptor signalling pathway and linked derailed immunomodulation: A study from Northeast India.
abstract: Preterm delivery (PTD) is one of the potent contributor of neonatal mortality and morbidity, and the underlying cause in some situation is elusive. This study attempts to delineate the association of deregulation in progesterone receptor (PR) pathway and deleterious immune responses in predisposing patients to PTD in Northeast India, a region with high rate of PTD cases. A total of 109 cases of PTD and 100 term delivery cases were enrolled with all clinical details. The PTD cases were stratified based on gestation age at delivery. The differential expression of PR and key downstream effectors and cytokines were evaluated for correlation with PTD susceptibility, gestational period, and pregnancy outcome. The results indicated a sharp downregulation in PR expression is associated with PTD susceptibility, lower gestational period and negative pregnancy outcome. The PR downstream effector PIBF was also found to be downregulated in PTD, and is associated with gestational period and negative pregnancy outcome. The downregulation of PR and PIBF expression was found to correlate with a predominant Th1 state with higher CD56+NK cell counts and pro-inflammatory burst lead by hyper TNF-α, NF-kB and IFNγ expression, and complicated by lower IL10 expression, contributing to PTD as well as negative pregnancy outcome in the PTD cases. TNF-α expression in placenta inversely correlated with placental PR expression. To conclude, deregulation in PR pathway is a hallmark of preterm delivery and negative pregnancy outcome. Differential expression of several markers such as PR, PIBF and TNF-α has prognostic significance, and hence is of clinical significance.
authors.affiliation: Department of Biological Science, Gauhati University, Guwahati, Assam, India; Department of Molecular Biology and Biotechnology, CCSU, Guwahati, Assam, India.
authors.forename: Diptika
authors.initials: D
authors.lastname: Tiwari
authors.affiliation: Department of Molecular Biology and Biotechnology, CCSU, Guwahati, Assam, India.
authors.forename: Purabi Deka
authors.initials: PD
authors.lastname: Bose
authors.affiliation: Department of Biological Science, Gauhati University, Guwahati, Assam, India.
authors.forename: Rizwana
authors.initials: R
authors.lastname: Sultana
authors.affiliation: Department of Biotechnology, Gauhati University, Guwahati, Assam, India; Guwahati Medical College Hospital (GMCH), Guwahati, Assam, India.
authors.forename: Chandana Ray
authors.initials: CR
authors.lastname: Das
authors.affiliation: Department of Biotechnology, Gauhati University, Guwahati, Assam, India. Electronic address: sujoy.bose@gauhati.ac.in.
authors.forename: Sujoy
authors.initials: S
authors.lastname: Bose
mesh_terms: D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D006801:Humans; D056747:Immunomodulation; D007194:India; D018836:Inflammation Mediators / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D007752:Obstetric Labor, Premature / Q000175:diagnosis* / Q000276:immunology; D011247:Pregnancy; D011256:Pregnancy Outcome; D011257:Pregnancy Proteins / Q000378:metabolism*; D011379:Prognosis; D011980:Receptors, Progesterone / Q000378:metabolism*; D015398:Signal Transduction; D013491:Suppressor Factors, Immunologic / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018836:Inflammation Mediators; D016328:NF-kappa B; C110058:PIBF1 protein, human; D011257:Pregnancy Proteins; D011980:Receptors, Progesterone; D013491:Suppressor Factors, Immunologic; D014409:Tumor Necrosis Factor-alpha
keywords: Cytokines; NK cells; Negative pregnancy outcome; Preterm delivery; Progesterone induced blocking factor; Progesterone receptor