Yin Bo, Liu Xishi, Guo Sun-Wei
1 Shanghai Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.
2 Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai, China.
Reprod Sci. 2018 Jul;25(7):1024-1036. doi: 10.1177/1933719118756755. Epub 2018 Feb 13.
Caloric restriction (CR) has been demonstrated to have many health-beneficial effects in many species, but whether CR can impede the development of endometriosis is unknown. To test the hypothesis that CR can impede the growth of endometriotic lesions and fibrogenesis, we conducted 2 experiments. In experiment 1, 20 female Balb/C mice were randomly assigned to either ad libitum (AL) group that was fed AL or to CR group that was fed 30% less calories than that of AL mice. Two weeks after the implementation of the dietary intervention, endometriosis was induced by intraperitoneal injection of endometrial fragments. Two weeks after the induction, all mice were sacrificed and their lesion samples were evaluated. In experiment 2, another 20 mice were used and CR was implemented 2 weeks after induction of endometriosis and lasted for 4 weeks. Caloric restriction instituted before the induction of endometriosis reduced the lesion weight by 88.5%, whereas CR implemented well after lesions were established reduced the lesion weight by 93.0%. In both cases, CR significantly increased staining levels of markers of autophagy but reduced proliferation, angiogenesis, steroidogenesis, and fibrosis in lesions as compared with the AL group. Consequently, CR, instituted either before or after the induction of endometriosis, dramatically curbs the growth of endometriotic lesions and fibrogenesis through multiple mechanisms. Caloric restriction and CR mimetics, a family of compounds mimicking the beneficial effect of CR, even when instituted well after lesions are established, may stall the development of endometriosis. Given the scarcity in research on how lifestyle can impact on the development of endometriosis, our study should hopefully stimulate more research in this area.
热量限制（CR）已被证明在许多物种中具有许多有益健康的作用，但CR是否能阻碍子宫内膜异位症的发展尚不清楚。为了验证CR可以阻碍子宫内膜异位症病变生长和纤维化的假设，我们进行了两项实验。在实验1中，将20只雌性Balb/C小鼠随机分为自由摄食（AL）组，即给予自由摄食，或分为CR组，给予比AL组小鼠少30%热量的食物。在饮食干预实施两周后，通过腹腔注射子宫内膜碎片诱导子宫内膜异位症。诱导两周后，处死所有小鼠并评估其病变样本。在实验2中，使用另外20只小鼠，在子宫内膜异位症诱导后两周实施CR，并持续4周。在子宫内膜异位症诱导前实施热量限制可使病变重量减轻88.5%，而在病变形成后很久实施CR可使病变重量减轻93.0%。在这两种情况下，与AL组相比，CR均显著提高了自噬标志物的染色水平，但降低了病变中的增殖、血管生成、类固醇生成和纤维化。因此，在子宫内膜异位症诱导之前或之后实施CR，均可通过多种机制显著抑制子宫内膜异位症病变的生长和纤维化。热量限制和CR模拟物，一类模拟CR有益作用的化合物，即使在病变形成后很久实施，也可能延缓子宫内膜异位症的发展。鉴于关于生活方式如何影响子宫内膜异位症发展的研究较少，我们的研究有望激发该领域更多的研究。
