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

Capsule:
Proteomic analysis of neurotrophins within the functional layer of the endometrium identified two factors that are expressed differentially in the eutopic endometrium of women with endometriosis compared to controls.

Authors:
Aimee S. Browne, M.D., M.Sc., Jie Yu, M.D., M.Sc., Ruo-Pan Huang, M.D., Ph.D., Antônio M. C. Francisco, M.D., Neil Sidell, Ph.D., Robert N. Taylor, M.D., Ph.D.

Volume 98, Issue 3, Pages 713-719, September 2012

Abstract:

Objective:
To evaluate neurotrophin (NT) expression in the endometrium of women with and 40 without endometriosis

Design:
Prospective, cross-sectional, translational study

Setting:
Academic hospital

Patient(s):
Thirty-three reproductive age women undergoing laparoscopy for infertility, pelvic pain, intramural fibroids, or tubal ligation

Intervention(s):
Endometrial biopsies, protein microarrays, RT-PCR, ELISAs and Western blotting

Main Outcome Measures:
Neurotrophin proteins and mRNAs in eutopic endometrial biopsies

Results:
Among seven neurotrophic proteins detected on the antibody microarrays, RT-PCR analysis confirmed nerve growth factor (NGF), NT-4/5, and brain-derived neurotrophic factor (BDNF) mRNAs in endometrial tissue. Quantitative ELISAs revealed that NT-4/5 (806 ± 701 vs. 256 ± 190 pg/100 mg protein, P=0.04) and BDNF (121 ± 97 vs. 14 ± 11 ng/100 mg protein, P

Conclusions:
Neurotrophins are synthesized in situ within the endometrium. NT-4/5 and BDNF proteins were more concentrated in biopsies from endometriosis cases than controls, whereas NGF levels were similar. We hypothesize that the local production of NTs induces sensory innervation of endometrium of women with endometriosis. These NTs represent novel targets for the diagnosis and treatment of endometriosis.

  • Raul Gomez, PhD, IUIVI

    Congrats to the authors for such a novel
    and interesting report and specially for the challenging hypothesis they
    propose. On of the most remarkable hints is the huge effort taken by the
    authors to prove with no doubt their point that specific NT factors identified
    (by the way, do the RayBiotech panels cover all the existing Neurotropins?) are
    increased in the eutopic endometrium of women with endometriosis. For such
    purposes they have double-checked the amount of protein with two different
    quantitative techniques. By employing RT-PCR the authors have shown that very
    likely the endometrium itself is a source of NT rather that a merely acceptors
    of circulating ones. Such analysis does not however exclude the possibility
    that differences observed for NT are debt to systemic rather than local
    production. Therefore in my humble opinion the study had benefited form
    performing quantitative (rather than not quantitative) RT-PCR in order to
    clarify this point.

    Anyway, whether local or systemic the
    increased expression of NT in eutopic endometrium of endometriosis has thrown
    challenging new questions, we would greatly appreciate if the authors might
    discuss them.

    1) The fact that NT were increased in
    only the endometriosis group but not in the control despite both of them
    experience pain, might perhaps point to the fact that NT are involved in
    endometriosis implantation, growth and development but not related to pain?.

    2) Even more increased innervation is
    observed in the ectopic endometrium pointing to the clear implication of this
    phenomenon in endometriosis, but is there any rationale to expect that neurogenesis
    be a consequence rather than a cause of endometriosis? Might perhaps the the
    authors speculate on how “deregulation” of neuroangiogenesis contribute to the
    development of endometriosis? In the context of the neuoroangiogenesis hypothesis should we
    expect inhibition of angiogenesis in the ectopic endometrium by using
    inhibitors of nerve growth?

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