Brain-Derived Neurotrophic Factor in Plasma of Women with Endometriosis

Abstract

Purpose Endometriosis is one of the most common benign gynecological diseases affecting women of reproductive age; it is characterized by the presence and growth of ectopic endometrial tissue outside the endometrial cavity. This complex disease is frequently associated with infertility and pelvic pain. Given the relationship and the apparent importance of the role that neurotrophins play in the reproductive system, and in particular brain-derived neurotrophic factor (BDNF) which is involved in both the central and peripheral pain pathways, we were interested in determining whether the presence of endometriosis is associated and correlated with plasma and follicular fluid variation of BDNF. Methods We determined BDNF level in plasma and in follicular fluid from infertile women with endometriosis and fertile women without the disease. Results BDNF plasma levels were significantly higher in endometriotic patients than in control women (p<0.001). After surgery this level decreased significantly (p<0.001), ranging within the values of control women in follicular phase. In follicular fluid, BDNF values were significantly lower in infertile women for endometriosis than in infertile women for male factors (p<0.001). Conclusion These data raise the possibility that neuroinflammatory reactions in endometriosis could have a neuroprotective effect and support the hypothesis that BDNF represents an important link in the networks of human homeostasis, thus providing an early marker for patients affected by endometriosis. Moreover, low BDNF levels in follicular fluid may refect an altered ovary production and may be a marker of poor oocyte quality and poor fertility in women suffering from endometriosis.

Proteomic identification of neurotrophins in the eutopic endometrium of women with endometriosis

“…Based on the microarray signal intensity and reports of NT expression in the literature (21, 26), we selected the three most prominent (NGF, NT-4/5 and BDNF), for RT-PCR analyses, quantitative ELISAs and Western blotting.…”

The Impact of Endometriosis across the Lifespan of Women: Foreseeable Research and Therapeutic Prospects

“…Unfortunately, measurement of nerve fiber density requires an endometrial biopsy and thus is more technically demanding, painful, time consuming, and resource intensive than a simple blood test and is therefore potentially less appealing to women and their health care providers. In contrast, mean plasma concentrations of the neurotrophin, brain derived neurotrophic factor (BDNF), were greater than 2 times higher in women with endometriosis versus healthy asymptomatic controls whilst no differences were found at three months after surgical removal of lesions [ 75 ]. Moreover, increased expression of BDNF and neurotrophin 4/5 has been demonstrated in the endometrium of women with endometriosis versus healthy controls [ 76 ].…”

Factors affecting stability of plasma brain-derived neurotrophic factor

“…The clinical utility of circulating concentrations of BDNF have been explored in neuropsychiatric disorders such as obsessive compulsive disorder 4 , eating disorders 5 , depression 6 – 9 , schizophrenia 10 , bipolar disorder 9 , 11 , 12 , as well as neurodegenerative diseases including Parkinson’s, Huntington’s, and Alzheimer’s disease 13 , 14 . Furthermore, increased circulating BDNF concentrations relative to controls have been linked with several different cancers 15 – 17 and gynecological disorders including polycystic ovarian syndrome 18 and endometriosis 19 – 21 . Indeed, women with endometriosis have elevated circulating BDNF concentrations compared to women without disease 19 – 21 , which correlated with pelvic pain 21 , and decreased after surgical removal of lesions 19 .…”

“…Furthermore, increased circulating BDNF concentrations relative to controls have been linked with several different cancers 15 – 17 and gynecological disorders including polycystic ovarian syndrome 18 and endometriosis 19 – 21 . Indeed, women with endometriosis have elevated circulating BDNF concentrations compared to women without disease 19 – 21 , which correlated with pelvic pain 21 , and decreased after surgical removal of lesions 19 . However the clinical value of BDNF as a marker of endometriosis has also been challenged 21 , 22 .…”

“…However the clinical value of BDNF as a marker of endometriosis has also been challenged 21 , 22 . While some studies find BDNF to be a useful clinical marker of endometriosis or certain endometriotic lesion types 19 – 21 , others find the difference in BDNF between women with and without endometriosis is not predictive of disease 21 , 22 . The reasons for variable and divergent findings between studies is difficult to resolve, but could include the fact that some studies quantified BDNF in plasma whilst others used serum, or that different ELISA kits were used for quantification.…”