title: Identification of key contributory factors responsible for vascular dysfunction in idiopathic recurrent spontaneous miscarriage.
abstract: Poor endometrial perfusion during implantation window is reported to be one of the possible causes of idiopathic recurrent spontaneous miscarriage (IRSM). We have tested the hypothesis that certain angiogenic and vasoactive factors are associated with vascular dysfunction during implantation window in IRSM and, therefore, could play a contributory role in making the endometrium unreceptive in these women. This is a prospective case-controlled study carried out on 66 women with IRSM and age and BMI matched 50 fertile women serving as controls. Endometrial expression of pro-inflammatory (IL-1β, TNF-α, IFN-γ, TGF-β1), anti-inflammatory (IL-4, -10), angiogenesis-associated cytokines (IL-2, -6, -8), angiogenic and vasoactive factors including prostaglandin E2 (PGE2), vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), nitric oxide (NO) and adrenomedullin (ADM) were measured during implantation window by ELISA. Subendometrial blood flow (SEBF) was assessed by color Doppler ultrasonography. Multivariate analysis was used to identify the significant factor(s) responsible for vascular dysfunction in IRSM women during window of implantation and further correlated with vascular dysfunction. Endometrial expression of pro-inflammatory cytokines and PGE2 were up-regulated and anti-inflammatory and angiogenesis-associated cytokines down-regulated in IRSM women as compared with controls. Further, the angiogenic and vasoactive factors including VEGF, eNOS, NO and ADM were found to be down-regulated and SEBF grossly affected in these women. Multivariate analysis identified IL-10, followed by VEGF and eNOS as the major factors contributing towards vascular dysfunction in IRSM women. Moreover, these factors strongly correlated with blood flow impairment. This study provides an understanding that IL-10, VEGF and eNOS are the principal key components having a contributory role in endometrial vascular dysfunction in women with IRSM. Down-regulation of these factors is also associated with impaired endometrial perfusion which possibly makes the endometrium unreceptive that may eventually cause early pregnancy loss.
authors.affiliation: School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Banerjee
authors.forename: Sanghamitra
authors.initials: S
authors.lastname: Ghosh
authors.forename: Mainak
authors.initials: M
authors.lastname: Dutta
authors.forename: Elavarasan
authors.initials: E
authors.lastname: Subramani
authors.forename: Jaydeep
authors.initials: J
authors.lastname: Khalpada
authors.forename: Sourav
authors.initials: S
authors.lastname: Roychoudhury
authors.forename: Baidyanath
authors.initials: B
authors.lastname: Chakravarty
authors.forename: Koel
authors.initials: K
authors.lastname: Chaudhury
mesh_terms: D000026:Abortion, Habitual / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D053607:Adrenomedullin / Q000235:genetics / Q000378:metabolism; D000328:Adult; D016022:Case-Control Studies; D015232:Dinoprostone / Q000378:metabolism; D010064:Embryo Implantation; D004717:Endometrium / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism; D015999:Multivariate Analysis; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D011446:Prospective Studies; D014463:Ultrasonography; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: C508609:IL10 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016753:Interleukin-10; D053607:Adrenomedullin; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D015232:Dinoprostone