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Pathogenetic Mechanisms of Deep Infiltrating Endometriosis

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Abstract

Endometriosis is a benign gynecologic disease, affecting women of reproductive age associated with chronic pelvic pain, dysmenorrhea, dyspareunia and infertility. Ovarian endometrioma (OMA), superficial peritoneal endometriosis (SPE), and deep infiltrating endometriosis (DIE) are, till now, recognized as major phenotypes. The discussion is to know whether they share the same pathogenetic mechanisms. Till today, DIE is recognized as the most severe clinical form of endometriosis and has a complex clinical management. The DIE lesions have been considered in the present article, without distinguishing between the anterior (bladder) or the posterior (vagina, uterosacral ligaments, rectum, and ureter) compartment. The present knowledge indicates that hormonal function (estrogen and progesterone receptors) and immunological factors, such as peritoneal macrophages, natural killer cells, and lymphocytes, are critically altered in DIE. The aggressive behavior of DIE may be explained by the highly decreased apoptosis (nuclear factor kappa-light-chain-enhancer of activated B cells [NF-kB], B-cell lymphoma 2 [Blc-2], and anti-Mullerian hormone) and by the increased proliferation activity related to oxidative stress (NF-kB, reactive oxygen species, extracellular regulated kinase (ERK), advanced oxidation protein product). Invasive mechanisms are more expressed (matrix metalloproteinases and activins) in DIE in comparison to the OMA and SPE. Correlated with the increased invasiveness are the data on very high expression of neuroangiogenesis (nerve growth factor, vascular endothelial growth factor, and intercellular adhesion molecule) genes in DIE. Therefore, at the present time, several of the DIE pathogenetic features result specific in comparison to other endometriosis phenotypes, pleading for the existence of a specific entity. These evidence of specific pathogenetic features of DIE may explain the more severe symptomatology related to this form of endometriosis and suggest possible future target medical treatments.

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Authors and Affiliations

  1. Obstetrics and Gynecology, Department of Molecular and Developmental Medicine, S. Maria alle Scotte, University of Siena, viale Bracci 53100, Siena, Italy

    Claudia Tosti MD, Serena Pinzauti MD & Felice Petraglia MD

  2. Department of Gynecology Obstetrics II and Reproductive Medicine, Faculté de Médecine, AP-HP, Hôspital Cochin, Université Paris Descartes, Sorbonne Paris Cité, Paris, France

    Claudia Tosti MD, Serena Pinzauti MD, Pietro Santulli MD, PhD & Charles Chapron MD

  3. Institut Cochin, Université Paris Descartes, Sorbonne Paris Cité, CNRS (UMR 8104), Paris, France

    Pietro Santulli MD, PhD & Charles Chapron MD

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  1. Claudia Tosti MD
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  2. Serena Pinzauti MD
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  5. Felice Petraglia MD
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Correspondence to Felice Petraglia MD.

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Tosti, C., Pinzauti, S., Santulli, P. et al. Pathogenetic Mechanisms of Deep Infiltrating Endometriosis. Reprod. Sci. 22, 1053–1059 (2015). https://doi.org/10.1177/1933719115592713

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