Innervation of ectopic endometrium in a rat model of endometriosis

Karen J. Berkley, Natalia Dmitrieva, Kathleen S. Curtis, Raymond E. Papka

Research output: Contribution to journalArticle

157 Citations (Scopus)

Abstract

Endometriosis (ENDO) is a disorder in which vascularized growths of endometrial tissue occur outside the uterus. Its symptoms include reduced fertility and severe pelvic pain. Mechanisms that maintain the ectopic growths and evoke symptoms are poorly understood. One factor not yet considered is that the ectopic growths develop their own innervation. Here, we tested the hypothesis that the growths develop both an autonomic and a sensory innervation. We used a rat model of surgically induced ENDO whose growths mimicthose in women. Furthermore, similar to women with ENDO, such rats exhibit reduced fertility and increased pelvic nociception. The ENDO was induced by autotransplanting, on mesenteric cascade arteries, small pieces of uterus that formed vascularized cysts. The cysts and healthy uterus were harvested from proestrous rats and immunostained using the pan-neuronal marker PGP9.5 and specific markers for calcitonin gene-related peptide (CGRP) (sensory C and Aσ fibers), substance P (SP) (sensory C and Aσ fibers) and vesicular monoamine transporter (sympathetic fibers). Cysts (like the uterus) were robustly innervated, with many PGP9.5-stained neurites accompanying blood vessels and extending into nearby luminal epithelial layers. CGRP-, SP-, and vesicular monoamine transporter-immunostained neurites also were observed, with CGRP and SP neurites extending the furthest into the cyst lining. These results demonstrate that ectopic endometrial growths develop an autonomic and sensory innervation. This innervation could contribute not only to symptoms associated with ENDO but also to maintenance of the ectopic growths.

Original languageEnglish
Pages (from-to)11094-11098
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number30
DOIs
StatePublished - 27 Jul 2004

Fingerprint

Endometriosis
Endometrium
Growth
Uterus
Calcitonin Gene-Related Peptide
Cysts
Neurites
Substance P
Vesicular Monoamine Transport Proteins
Myelinated Nerve Fibers
Unmyelinated Nerve Fibers
Fertility
Adrenergic Fibers
Mesenteric Arteries
Pelvic Pain
Nociception
Blood Vessels
Maintenance

Keywords

  • Fertility
  • Neuropeptides
  • Pain
  • Transplant
  • Uterus

Cite this

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abstract = "Endometriosis (ENDO) is a disorder in which vascularized growths of endometrial tissue occur outside the uterus. Its symptoms include reduced fertility and severe pelvic pain. Mechanisms that maintain the ectopic growths and evoke symptoms are poorly understood. One factor not yet considered is that the ectopic growths develop their own innervation. Here, we tested the hypothesis that the growths develop both an autonomic and a sensory innervation. We used a rat model of surgically induced ENDO whose growths mimicthose in women. Furthermore, similar to women with ENDO, such rats exhibit reduced fertility and increased pelvic nociception. The ENDO was induced by autotransplanting, on mesenteric cascade arteries, small pieces of uterus that formed vascularized cysts. The cysts and healthy uterus were harvested from proestrous rats and immunostained using the pan-neuronal marker PGP9.5 and specific markers for calcitonin gene-related peptide (CGRP) (sensory C and Aσ fibers), substance P (SP) (sensory C and Aσ fibers) and vesicular monoamine transporter (sympathetic fibers). Cysts (like the uterus) were robustly innervated, with many PGP9.5-stained neurites accompanying blood vessels and extending into nearby luminal epithelial layers. CGRP-, SP-, and vesicular monoamine transporter-immunostained neurites also were observed, with CGRP and SP neurites extending the furthest into the cyst lining. These results demonstrate that ectopic endometrial growths develop an autonomic and sensory innervation. This innervation could contribute not only to symptoms associated with ENDO but also to maintenance of the ectopic growths.",
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Innervation of ectopic endometrium in a rat model of endometriosis. / Berkley, Karen J.; Dmitrieva, Natalia; Curtis, Kathleen S.; Papka, Raymond E.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 30, 27.07.2004, p. 11094-11098.

Research output: Contribution to journalArticle

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AU - Berkley, Karen J.

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