PMID- 27049074
OWN - NLM
STAT- MEDLINE
DCOM- 20160707
LR  - 20211203
IS  - 0393-974X (Print)
IS  - 0393-974X (Linking)
VI  - 30
IP  - 1
DP  - 2016 Jan-Mar
TI  - The role of NADPH-derived reactive oxygen species production in the pathogenesis 
      of endometriosis: a novel mechanistic approach.
PG  - 31-40
AB  - Endometriosis is defined as endometriotic tissue growing outside the uterine 
      cavity. It is a common gynecological disorder in women of reproductive age and is 
      associated with chronic pelvic pain and infertility. Despite several studies and 
      theories to explain its cause, the exact pathogenesis of endometriosis remains 
      unclear. Retrograde menstruation is the most plausible theory, however, it is not 
      exclusive. The disparity between the actual prevalence of retrograde menstruation 
      and the prevalence of endometriosis suggests that other factors may determine the 
      susceptibility to endometriosis development. Oxidative stress has been associated 
      with endometriosis. This study aimed to explore the role of NADPH oxidase family 
      in the production of reactive oxygen species (ROS) and to determine whether ROS 
      induce the proliferation of endometriotic implants via mammalian target of 
      rapamycin (mTOR) signaling. Anonymous endometriotic tissue samples were collected 
      from women undergoing laparoscopy for endometriosis. The samples were stained 
      with dihydroethidium and fluorescent images of the slides were taken to detect 
      ROS production. After extraction of RNA from the samples and c-DNA generation, 
      quantitative real-time PCR, protein extraction and Western blot were performed to 
      study gene and protein expression of NADPH oxidase 1 (NOX 1), mTOR and 
      fibronectin. The results showed an increase in ROS levels and NOX 1 gene and 
      protein expression in the endometriotic tissues compared to the normal 
      surrounding tissue control. Also, mTOR and fibronectin, gene expression was found 
      to be increased. Up regulation of NOX at gene and protein level leads to 
      increased production of ROS in the endometriotic tissue, which in turn causes 
      proliferation of the ectopic tissue via alteration of the mTOR signaling pathway. 
      Increased fibronectin gene expression points towards tissue injury in 
      endometriosis as compared to the normal surrounding tissue. This manuscript adds 
      a new insight into the pathogenesis of endometriosis and serves as a background 
      for development of new treatments for the disease-associated pain and 
      infertility.
FAU - Nassif, J
AU  - Nassif J
AD  - Department of Obstetrics and Gynecology, Faculty of Medicine and Medical Center, 
      American University of Beirut, Beirut, Lebanon.
FAU - Abbasi, S A
AU  - Abbasi SA
AD  - Department of Obstetrics and Gynecology, Faculty of Medicine and Medical Center, 
      American University of Beirut, Beirut, Lebanon.
FAU - Nassar, A
AU  - Nassar A
AD  - Department of Obstetrics and Gynecology, Faculty of Medicine and Medical Center, 
      American University of Beirut, Beirut, Lebanon.
FAU - Abu-Musa, A
AU  - Abu-Musa A
AD  - Department of Obstetrics and Gynecology, Faculty of Medicine and Medical Center, 
      American University of Beirut, Beirut, Lebanon.
FAU - Eid, A A
AU  - Eid AA
AD  - Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American 
      University of Beirut, Beirut, Lebanon.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Italy
TA  - J Biol Regul Homeost Agents
JT  - Journal of biological regulators and homeostatic agents
JID - 8809253
RN  - 0 (Fibronectins)
RN  - 0 (Reactive Oxygen Species)
RN  - 11062-77-4 (Superoxides)
RN  - 53-59-8 (NADP)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Blotting, Western
MH  - Cell Proliferation
MH  - Endometriosis/*etiology/*metabolism/pathology
MH  - Female
MH  - Fibronectins/genetics/metabolism
MH  - Humans
MH  - NADP/*metabolism
MH  - NADPH Oxidases/metabolism
MH  - Oxidation-Reduction
MH  - Phosphorylation
MH  - Reactive Oxygen Species/*metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Signal Transduction
MH  - Superoxides/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
EDAT- 2016/04/07 06:00
MHDA- 2016/07/09 06:00
CRDT- 2016/04/07 06:00
PHST- 2016/04/07 06:00 [entrez]
PHST- 2016/04/07 06:00 [pubmed]
PHST- 2016/07/09 06:00 [medline]
AID - 4 [pii]
PST - ppublish
SO  - J Biol Regul Homeost Agents. 2016 Jan-Mar;30(1):31-40.