Cuevas Marielly, Cruz Myrella L, Ramirez Antonio E, Flores Idhaliz, Thompson Kenira J, Bayona Manuel, Vernon Michael W, Appleyard Caroline B
1 Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce, Puerto Rico.
2 Public Health Program, Ponce Research Institute, Ponce Health Sciences University, Ponce Research Institute, Ponce, Puerto Rico.
Reprod Sci. 2018 Mar;25(3):347-357. doi: 10.1177/1933719117737846. Epub 2017 Nov 6.
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.
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.
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.
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.
我们之前已经表明，诱导前的应激会使子宫内膜异位症大鼠模型的临床表现和炎症参数恶化。本研究旨在探讨子宫内膜异位症发展过程中的应激是否会通过神经生长和免疫改变影响异位内膜植入物的生长。
通过将子宫角植入物缝合到小肠系膜上，对雌性Sprague-Dawley大鼠进行手术诱导子宫内膜异位症。两周后，一组大鼠（子宫内膜异位症-应激组）接受为期10天的游泳应激方案。对照组无应激（子宫内膜异位症-无应激组）或仅接受缝合且无应激（假手术-应激组）。在第60天，处死所有大鼠并检查是否存在异位内膜小泡。测量每个小泡的大小。取出子宫和结肠，评估损伤、细胞浸润以及神经生长因子（NGF）、其受体（p75和原肌球蛋白受体激酶A（Trk-A）/磷酸化Trk-A）和降钙素基因相关肽（一种感觉纤维标志物）的表达。对腹腔液白细胞计数进行差异分析。
应激显著增加了异位内膜小泡的大小，但未增加结肠损伤，并增加了肥大细胞的浸润。在接受应激的子宫内膜异位症动物的子宫中，发现NGF及其受体的表达显著增加。
应激会刺激子宫内膜异位症动物模型中异位内膜小泡的发展，并增加炎症细胞向腹膜的募集。此外，应激会促进子宫中神经纤维的生长。
