Stress During Development of Experimental Endometriosis Influences Nerve Growth and Disease Progression

Marielly Cuevas, Myrella L. Cruz, Antonio E. Ramirez, Idhaliz Flores, Kenira J. Thompson, Manuel Bayona, Michael W. Vernon, Caroline B. Appleyard

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Purpose: We have previously shown that stress prior to induction worsens clinical presentation and inflammatory parameters in a rat model of endometriosis. This study was designed to examine whether stress during the development of endometriosis can affect the growth of endometriotic implants through nerve growth and immune alterations. Methods: Endometriosis was surgically induced in female Sprague-Dawley rats by suturing uterine horn implants onto the small intestine mesentery. Two weeks later, one group of rats (endo-stress) was subjected to a 10-day swim stress protocol. Controls had no stress (endo-no stress) or sutures only and stress (sham-stress). On day 60, all rats were killed and examined for the presence of endometriotic vesicles. The size of each vesicle was measured. The uterus and colon were removed and assessed for damage, cell infiltration, and expression of nerve growth factor (NGF), its receptors (p75 and Tropomyosin receptor kinase A (Trk-A)/pTrk-A), and calcitonin gene–related peptide, a sensory fiber marker. A differential analysis of peritoneal fluid white blood cell count was performed. Results: Stress significantly increased endometriotic vesicle size but not colonic damage and increased infiltration of mast cells. Significantly increased expression of NGF and its receptors was found in the uterus of animals with endometriosis receiving stress. Conclusions: Stress stimulates the development of ectopic endometrial vesicles in an animal model of endometriosis and increases inflammatory cell recruitment to the peritoneum. In addition, stress promotes nerve fiber growth in the uterus.

Original languageEnglish (US)
Pages (from-to)347-357
Number of pages11
JournalReproductive Sciences
Issue number3
StatePublished - Mar 1 2018
Externally publishedYes


  • Trk
  • endometriosis
  • nerve growth factor
  • p75
  • stress

ASJC Scopus subject areas

  • Obstetrics and Gynecology


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