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

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Abstract

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.

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Author information

Authors and Affiliations

  1. Department of Basic Sciences, Physiology Division, Medical School and Ponce Research Institute, Ponce Health Sciences University, PO Box 7004, Ponce, 00716, Puerto Rico

    Marielly Cuevas PhD, Myrella L. Cruz MT, Antonio E. Ramirez MD, Idhaliz Flores PhD, Kenira J. Thompson PhD, Manuel Bayona MD & Caroline B. Appleyard PhD

  2. Public Health Program, Ponce Research Institute, Ponce Health Sciences University, Ponce Research Institute, Ponce, Puerto Rico

    Manuel Bayona MD

  3. Department of Obstetrics and Gynecology, Center for Reproductive Medicine, West Virginia University, Morgantown, West Virginia, USA

    Michael W. Vernon PhD

Authors
  1. Marielly Cuevas PhD
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  2. Myrella L. Cruz MT
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  3. Antonio E. Ramirez MD
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  4. Idhaliz Flores PhD
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  5. Kenira J. Thompson PhD
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  6. Manuel Bayona MD
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  8. Caroline B. Appleyard PhD
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Corresponding author

Correspondence to Caroline B. Appleyard PhD.

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Cuevas, M., Cruz, M.L., Ramirez, A.E. et al. Stress During Development of Experimental Endometriosis Influences Nerve Growth and Disease Progression. Reprod. Sci. 25, 347–357 (2018). https://doi.org/10.1177/1933719117737846

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  • DOI: https://doi.org/10.1177/1933719117737846

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