Shanghai OB/GYN Hospital, Fudan University, Shanghai, 200011, China.
Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Fudan University, Shanghai, China.
Reprod Sci. 2020 Jul;27(7):1423-1435. doi: 10.1007/s43032-019-00117-1. Epub 2020 Apr 21.
We tested the hypothesis that enriched environment (EE), consisting of enlarged space, and increased physical activity and social interactions, hinders the development of endometriosis through attenuated adrenergic signaling, enhanced autophagy, and reduced leptin levels. Two mouse experiments were performed. In Experiment 1, 40 female Balb/C mice were randomly divided into four equal-sized groups, the SE (standard environment), EE, p-EE (EE instituted after endometriosis induction), and the d-EE (SE housing but received uterine fragments from EE donors) groups. Housing intervention was initiated 3 weeks before the induction of endometriosis and continued for 3 weeks after induction. In Experiment 2, 20 female mice were randomly divided into SE and EE groups, and the plasma leptin levels were measured. We measured lesion weight and hotplate latency and performed Masson trichrome staining as well as immunohistochemistry analysis of β2 adrenergic receptor (ADRB2), dopamine receptor D2 (DRD2), vascular endothelial growth factor (VEGF), and microtubule-associated protein light chain 3 (LC3). We found that EE reduced the lesion weight by 40.8% as compared with SE mice, but the reduction in p-EE and d-EE mice did not reach statistical significance. EE significantly reduced staining levels of ADRB2 and VEGF as well as the extent of lesional fibrosis but increased staining levels of LC3 and DRD2 in lesions as compared with the SE group. EE mice had reduced plasma leptin levels as compared with SE mice. Thus, EE decelerates the development of endometriosis and fibrogenesis and improved generalized hyperalgesia, possibly through increased DRD2 expression but decreased expression of ADRB2 and VEGF as well as enhanced autophagy and reduced leptin level.
我们检验了这样一个假设，即丰富环境（EE）通过减弱肾上腺素能信号、增强自噬和降低瘦素水平，阻碍内异症的发展，EE 由扩大空间、增加身体活动和社交互动组成。进行了两项小鼠实验。在实验 1 中，将 40 只雌性 Balb/C 小鼠随机分为四组，即 SE（标准环境）、EE、p-EE（内异症诱导后实施 EE）和 d-EE（SE 饲养但接受 EE 供体的子宫片段）组。饲养干预在诱导内异症前 3 周开始，并在诱导后继续 3 周。在实验 2 中，将 20 只雌性小鼠随机分为 SE 和 EE 组，并测量血浆瘦素水平。我们测量了病变重量和热板潜伏期，并进行了 Masson 三色染色以及β2 肾上腺素能受体（ADRB2）、多巴胺受体 D2（DRD2）、血管内皮生长因子（VEGF）和微管相关蛋白轻链 3（LC3）的免疫组化分析。我们发现，与 SE 小鼠相比，EE 使病变重量减少了 40.8%，但 p-EE 和 d-EE 小鼠的减少量未达到统计学意义。与 SE 组相比，EE 显著降低了 ADRB2 和 VEGF 的染色水平以及病变纤维化的程度，但增加了 LC3 和 DRD2 的染色水平。EE 小鼠的血浆瘦素水平低于 SE 小鼠。因此，EE 减缓了内异症和纤维化的发展，并改善了全身痛觉过敏，这可能是通过增加 DRD2 表达、降低 ADRB2 和 VEGF 表达以及增强自噬和降低瘦素水平来实现的。
