Torres-Reverón Annelyn, Rivera Leslie L, Flores Idhaliz, Appleyard Caroline B
1 Division of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce, Puerto Rico.
2 Department of Biomedical Sciences, Division of Neuroscience, School of Medicine, University of Texas at Rio Grande Valley, Edinburg, TX, USA.
Reprod Sci. 2018 Sep;25(9):1336-1348. doi: 10.1177/1933719117741374. Epub 2017 Nov 14.
Treatments for endometriosis include pharmacological or surgical procedures that produce significant side effects. We aimed to determine how environmental enrichment (EE) could impact the progression of endometriosis using the autotransplantation rat model. Female rats were exposed to EE (endo-EE: toys and nesting materials, 4 rats per cage, larger area enclosure) or no enrichment (endo-NE: 2 rats per cage) starting on postnatal day 21. After 8 weeks, sham surgery or surgical endometriosis was induced by suturing uterine horn tissue next to the intestinal mesentery, then allowed to progress for 60 days during which EE or NE continued. At the time of killing, we measured anxiety behaviors, collected endometriotic vesicles and uterus, and processed for quantitative real-time polymerase chain reaction for corticotropin-releasing hormone (CRH), urocortin-1, CRH receptors type 1 and type 2, and glucocorticoid receptor (GR). Endometriosis did not affect anxiety-like behaviors, yet rats in enriched conditions showed lower basal anxiety behaviors than the nonenriched group. Importantly, the endo-EE group showed a 28% reduction in the number of endometriosis vesicles and the vesicles were significantly smaller compared to the endo-NE group. Endometriosis increased CRH and GR only in the vesicles of endo-NE, and this increase was dampened in the endo-EE. However, urocortin 1 was increased in the vesicles of the endo-EE group, suggesting different pathways of activation of CRH receptors in this group. Our results suggest that the use of multimodal complementary therapies that reduce stress in endometriosis could be an effective and safe treatment alternative, with minimal side effects.
子宫内膜异位症的治疗方法包括药物治疗或手术治疗，但这些治疗会产生明显的副作用。我们旨在利用自体移植大鼠模型确定环境富集（EE）如何影响子宫内膜异位症的进展。从出生后第21天开始，将雌性大鼠置于EE环境（内膜-EE组：有玩具和筑巢材料，每笼4只大鼠，饲养区域较大）或无富集环境（内膜-NE组：每笼2只大鼠）中。8周后，通过将子宫角组织缝合在肠系膜旁进行假手术或诱导手术性子宫内膜异位症，然后让其发展60天，在此期间EE或NE环境持续存在。处死时，我们测量焦虑行为，收集子宫内膜异位症囊泡和子宫，并进行促肾上腺皮质激素释放激素（CRH）、尿皮质素-1、1型和2型CRH受体以及糖皮质激素受体（GR）的定量实时聚合酶链反应。子宫内膜异位症并未影响焦虑样行为，但处于富集环境中的大鼠的基础焦虑行为低于未富集组。重要的是，内膜-EE组的子宫内膜异位症囊泡数量减少了28%，且与内膜-NE组相比，囊泡明显更小。子宫内膜异位症仅在内膜-NE组的囊泡中增加了CRH和GR，而在内膜-EE组中这种增加受到了抑制。然而，尿皮质素1在内膜-EE组的囊泡中增加，表明该组中CRH受体的激活途径不同。我们的结果表明，使用多模式辅助疗法减轻子宫内膜异位症患者的压力可能是一种有效且安全的治疗选择，副作用最小。
