Origins of endo

From Endometriosis Update blog (lots of good info- check it out!!):

"Several studies have focused on characterising the endometrium of women with and without endometriosis and found that; yes the endometrium in women with endometriosis is indeed different. The endometrium from women with endometriosis appears to have a higher ability to survive, proliferate and invade, seemingly filling in the missing part of the retrograde menstruation theory.

But, like all great mystery stories, the case is never wrapped up in a neat little package so early on. In recent years more and more evidence is coming to the fore, challenging the theory of retrograde menstruation. In particular there is now quite a significant amount of evidence to show the displaced endometrium that defines endometriosis is, in fact, present before you were even born. There are also rare documented cases of endometriosis in men, women who cannot menstruate and non-menstruating primates; so clearly there is the need for some radical re-thinking.

Maybe we’ve had the whole thing upside-down; maybe it is not the endometrium that dictates the fate of endometriosis, but endometriosis that dictates the fate of the endometrium. A collaborative research effort has provided some evidence to this very end (you can read the full article here). The authors of this study experimentally induced endometriosis in baboons by injecting endometrial cells into the pelvic cavity and letting them form endometriotic implants. They then compared the expression of genes within the endometrium of the baboons with experimentally induced endometriosis and disease free baboons over the course of 16 months. What they found was that the presence of endometriosis (even in its very early stages) led to marked changes (a total of 4,331 genes were altered) in the normal endometrium.

This potentially turns accepted wisdom on its head, in that women with endometriosis are not born with a defective endometrium that gives rise to endometriosis via retrograde menstruation. Rather, if we are to take all the above evidence into account, it appears endometriosis is a condition you are born with that, when the endometriotic implants ‘mature’ lead to changes in the function of the normal endometrium, thus perhaps also accounting for the fertility issues women with endo suffer from." http://www.endo-update.blogspot.co.uk/.../turning-on-its...

Peritoneal endo lesions nerve fibers

"RESULT(S): Pain-conducting substance-P-positive nerve fibers were found to be directly colocalized with human peritoneal endometriotic lesions in 74.5% of all cases. The endometriosis-associated nerve fibers are accompanied by immature blood vessels within the stroma. Nerve growth factor and neutrophin-3 are expressed by endometriotic cells. Growth-associated protein 43, a marker of neural outgrowth and regeneration, is expressed in endometriosis-associated nerve fibers but not in existing peritoneal nerves. CONCLUSION(S): The data provide the first evidence of direct contact between sensory nerve fibers and peritoneal endometriotic lesions. This implies that the fibers play an important role in the etiology of endometriosis-associated pelvic pain. Moreover, emerging evidence suggests that peritoneal endometriotic cells exhibit neurotrophic properties." http://www.ncbi.nlm.nih.gov/pubmed/17412328

 

"RESULT(S): Peritoneal endometriosis-associated nerve fibers were found significantly more frequently in group A than in group B (82.6% vs. 33.3%). CONCLUSION(S): The present study suggests that the presence of endometriosis-associated nerve fibers in the peritoneum is important for the development of endometriosis-associated pelvic pain and dysmenorrhea." http://www.ncbi.nlm.nih.gov/pubmed/18980761

 

"RESULT(S): Lesions from the rectovaginal septum were significantly more likely to be associated with a nerve fiber and report more menstrual pain than lesions from other regions. The PF glycodelin concentrations were also significantly higher in samples with an endometriotic-associated nerve. In peritoneal endometriotic lesions significantly more menstrual pain was reported when endometriotic lesions were associated with nerve fibers, although no difference was observed between the cytokine concentrations. Ovarian endometriotic lesions were rarely associated with nerve fibers.
CONCLUSION(S):
The presence of endometriosis-associated nerve fibers appear to be related to both the pain experienced by women with endometriosis and the concentration of PF cytokines; however, this association varies with the lesion location." http://www.ncbi.nlm.nih.gov/pubmed/22154765


"There was no difference in the density of nerve fibers across the menstrual cycle in peritoneal endometriotic lesions. These findings may explain why patients with peritoneal endometriosis often have painful symptoms throughout the menstrual cycle." http://www.ncbi.nlm.nih.gov/pubmed/21334610


"Progestogens and combined oral contraceptives reduced nerve fiber density and nerve growth factor and nerve growth factor receptor p75 expression in peritoneal endometriotic lesions." http://www.ncbi.nlm.nih.gov/pubmed/18976764

"Pain generation in EM is an intricate interplay of several factors such as the endometriotic lesions themselves and the pain-mediating substances, nerve fibres and cytokine-releasing immune cells such as macrophages. These interactions seem to induce a neurogenic inflammatory process. Recently published data demonstrated an increased peptidergic and decreased noradrenergic nerve fibre density in peritoneal lesions. These data could be substantiated by in vitro analyses demonstrating that the peritoneal fluids of patients suffering from EM induced an enhanced sprouting of sensory neurites from chicken dorsal root ganglia and decreased neurite outgrowth from sympathetic ganglia. These findings might be directly involved in the perpetuation of inflammation and pain. Furthermore, the evidence of EM-associated smooth muscle-like cells seems another important factor in pain generation. The peritoneal endometriotic lesion leads to reactions in the surrounding tissue and, therefore, is larger than generally believed. The identification of EM-associated nerve fibres and smooth muscle-like cells fuel discussions on the mechanisms of pain generation in EM, and may present new targets for innovative treatments." http://www.ncbi.nlm.nih.gov/pubmed/24590000

"We could detect an increased sensory and decreased sympathetic nerve fibres density in peritoneal lesions compared to healthy peritoneum. Peritoneal fluids of patients with endometriosis compared to patients without endometriosis induced an increased sprouting of sensory neurites from DRG and decreased neurite outgrowth from sympathetic ganglia. In conclusion, this study demonstrates an imbalance between sympathetic and sensory nerve fibres in peritoneal endometriosis, as well as an altered modulation of peritoneal fluids from patients with endometriosis on sympathetic and sensory innervation which might directly be involved in the maintenance of inflammation and pain." http://www.ncbi.nlm.nih.gov/pubmed/21888965

   

March is Endometriosis Awareness month!

 

March is endometriosis awareness month and yellow is the color! Here are a few pictures that I have run across that are useful for profile pictures, cover photos, and general awareness:

 

? Link Between PCOS and endometriosis

Old (from 1989): "Pelvic endometriosis was observed in 15 of 91 women (16.5%) with laparoscopically confirmed polycystic ovary syndrome. There were no significant clinical differences among those with and those without endometriosis. The groups were of similar age, parity, and ponderal indices and had similar incidences of oligomenorrhea, hirsutism, and infertility; the serum concentrations of LH, FSH, LH/FSH, prolactin, testosterone, and dehydroepiandrosterone sulfate were also similar in each group. However, women with polycystic ovaries and endometriosis presented more frequently with regular menses (40 versus 14.5%; P = .05) and less frequently with secondary amenorrhea (0 versus 38.2%; P = .05) and galactorrhea (0 versus 9.2%; P = .05) than the women with polycystic ovaries alone. Endometriosis appears to be a coincidental finding in polycystic ovary syndrome, and its development does not modify significantly the clinical picture or biochemical profiles of these patients. However, menstrual patterns seem to be affected." http://www.ncbi.nlm.nih.gov/pubmed/2797642

2011: "The endocrinologic and metabolic abnormalities of women with polycystic ovary syndrome (PCOS) can result in a series of endometrial diseases. Abnormalities of hyperandrogenism and hyperinsulinemia that may be found in PCOS can elevate the levels of E2 indirectly, reduce progesterone secretion and induce some growth factors such as vascular endothelial growth factor (VEGF) and insulin-like growth factors (IGFs) over expression, which may have a major impact on endometriosis occurrence and development. We suppose that there is a possible connection between PCOS and endometriosis." http://www.sciencedirect.com/.../pii/S1001784412600133

Surgical Technique and "microscopic" endo

"Occult or microscopic lesions have been reported as early as 1986 from laparotomy procedures. Hopton and Redwine {7} have shown a linear inverse relationship between the distance of the viewing lens from the peritoneal surface and the incidence of OME; these authors claim that OME almost ceases to exist with close contact laparoscopy with less than 1cm separation of the laparoscope tip from the peritoneal surface (and with direct visualisation laparoscopy, suggesting that the use of video-assisted laparoscopy may impair visualisation) with incidences of OME ranging from 0% to 25% in various studies {1-7}. 

 

"Hopton and Redwine {7} have also highlighted the key factors that are likely to be influential on whether OME is diagnosed: the definition of normal peritoneum, the size and location of biopsies of 'normal peritoneum', the histological definition of endometriosis, and whether women undergoing laparoscopic assessment have recently been using hormonal suppressive therapy....

 

"The more careful the search for endometriosis – and the closer the laparoscope tip is applied to the peritoneal surface – the less chance of missing any endometriosis. - There is a strong place for clear definitions to standardise laparoscopy performed by all gynaecological surgeons in relation to (a) viewing distance from the laparoscope tip and (b) definitions of what constitutes abnormal peritoneum, particularly the subtle abnormalities highlighted by Redwine {5} and Redwine and Yocom {6}. The more meticulous the search for endometriosis and the combination of this search with meticulous excision of all lesions, the more likely endometriosis is to be eradicated through laparoscopic surgery."

http://f1000.com/prime/718213409

Epigenetics in endo

Here is an interesting article discussing epigenetics in endometriosis. While they do assimilate epigenetics with pathogenesis of endo (since endo has been seen in fetuses, it is still more plausible that it is laid down embryonically), the incidence of epigenetics playing a role in how the disease presents itself and is influenced is interesting to consider.

 

 

http://molehr.oxfordjournals.org/content/15/10/587.long

 

 

Here's a tidbit:

 

"Endometriosis has been regarded as an ultimate hormonal disease, owing much to its estrogen-dependency and aberrations in estrogen production and metabolism (Bulun et al., 2002; Kitawaki et al., 2002; Gurates and Bulun, 2003). It also has been viewed as an immunological disease due to a myriad immunological aberration in endometriosis (Paul Dmowski and Braun, 2004; Ulukus and Arici, 2005). In addition, it has been thought of a disease caused by exposure to environmental pollution and toxins (Rier et al., 1993; Rier, 2002) although so far there are no solid human data (Guo, 2004). Finally, it has been regarded as a genetic disease (Simpson et al., 2003; Barlow and Kennedy, 2005), due, apparently, to its reported familial aggregation. Yet even the reported familial aggregation, when examined closely, may be debatable (Di and Guo, 2007), and there has been little progress regarding the identification of genetic variants that predispose women to endometriosis (Di and Guo, 2007; Falconer et al., 2007; Guo, 2009b)."

 

((((((NOTE: some of the references are dated- such as little progress to genetic variances when there have been such since then (2007).)))))

 

"Given the reported epigenetic aberrations in endometriosis, one question is whether these aberrations are the cause or merely the consequence of endometriosis. Since most, if not all, human studies reporting epigenetic aberrations in endometriosis are carried out cross-sectionally, the reported aberration may be a cause for, but also could be a consequence of, endometriosis.

 

"Aging (Wilson and Jones, 1983; Toyota and Issa, 1999; Richardson, 2002), diet (Jacob et al., 1998), chronic inflammation (Hsieh et al., 1998; Issa et al., 2001), prolonged transcriptional suppression (Song et al., 2002; Stirzaker et al., 2004) and even maternal care (Champagne et al., 2006). In endometriosis, it has been shown that prolonged stimulation of an endometriotic epithelial-like cell line by tumor necrosing factor (TNFα), which has been shown to have increased production in endometriosis, resulted in at least partial methylation in the PR-B promoter (Wu et al., 2008b). This provides evidence that certain phenotypic changes in endometriosis, such as increased production of proinflammatory cytokines, may also cause epigenetic aberrations, which in turn result in changes in gene expression and subsequently other phenotypic changes such as increased cellular proliferation (Wu et al., 2008a) and perhaps some phenotypic changes."

 

http://molehr.oxfordjournals.org/content/15/10/587.long

 

genotypes of GSTM1 and/or GSTT1 contribute to risk of endometriosis

"Endometriosis is one of the most frequent benign gynecological disorders. Numerous studies have shown an association between GSTM1 and/or GSTT1 polymorphisms and endometriosis susceptibility. However, these associations remain inconclusive. To derive a more precise estimation, we conducted a comprehensive search to identify all existing studies and then performed a meta-analysis. Electronic literature searches of the PubMed, Chinese Biomedical, and China National Knowledge Infrastructure databases were performed up to December 2013. GSTM1-, GSTT1-, and dual-null genotypes were analyzed independently, and pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated by comparing the null genotype with other genotypes using the random-effects or fixed-effects model. Twenty-five and 16 independent studies on GSTM1 and GSTT1 polymorphisms, respectively, and five GSTM1-GSTT1 interaction analyses were identified and included in this meta-analysis. Both GSTM1- and GSTT1-null genotypes increased risk of endometriosis (OR = 1.54, 95% CI: 1.30–1.83, P<0.001; OR = 1.41, 95% CI: 1.10–1.82, P = 0.007; respectively). Moreover, we found a significant positive association between the dual null genotype GSTM1-GSTT1 and endometriosis susceptibility (OR = 1.33, 95% CI: 1.03–1.72, P = 0.027). This meta-analysis provides evidence that null genotypes of GSTM1 and/or GSTT1 contribute to risk of endometriosis. Further investigations are required to confirm these findings." http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0106761