MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK.
J Endocrinol. 2021 May;249(2):71-82. doi: 10.1530/JOE-20-0446.
Heavy menstrual bleeding is common and debilitating but the causes remain ill defined. Rates of obesity in women are increasing and its impact on menstrual blood loss (MBL) is unknown. Therefore, we quantified BMI and MBL in women not taking hormones and with regular menstrual cycles and revealed a positive correlation. In a mouse model of simulated menstruation, diet-induced obesity also resulted in delayed endometrial repair, a surrogate marker for MBL. BrdU staining of mouse uterine tissue revealed decreased proliferation during menstruation in the luminal epithelium of mice on a high-fat diet. Menstruation is known to initiate local endometrial inflammation and endometrial hypoxia; hence, the impact of body weight on these processes was investigated. A panel of hypoxia-regulated genes (VEGF, ADM, LDHA, SLC2A1) showed consistently higher mean values in the endometrium of women with obesity and in uteri of mice with increased weight vs normal controls, although statistical significance was not reached. The inflammatory mediators, Tnf and Il6 were significantly increased in the uterus of mice on a high-fat diet, consistent with a pro-inflammatory local endometrial environment in these mice. In conclusion, obesity was associated with increased MBL in women. Mice given a high-fat diet had delayed endometrial repair at menstruation and provided a model in which to study the influence of obesity on menstrual physiology. Our results indicate that obesity results in a more pro-inflammatory local endometrial environment at menstruation, which may delay endometrial repair and increase menstrual blood loss.
月经过多是常见且令人虚弱的问题，但病因仍不明确。女性肥胖率正在上升，但其对月经失血（MBL）的影响尚不清楚。因此，我们在不服用激素且月经周期正常的女性中定量了 BMI 和 MBL，发现两者呈正相关。在模拟月经的小鼠模型中，饮食诱导的肥胖也导致了子宫内膜修复延迟，这是 MBL 的替代标志物。用 BrdU 对小鼠子宫组织进行染色，发现高脂肪饮食小鼠的腔上皮细胞在月经期间增殖减少。已知月经会引发局部子宫内膜炎症和缺氧；因此，我们研究了体重对这些过程的影响。一组缺氧调节基因（VEGF、ADM、LDHA、SLC2A1）在肥胖女性的子宫内膜和体重增加的小鼠子宫中的平均值明显更高，尽管未达到统计学意义。促炎介质 Tnf 和 Il6 在高脂肪饮食小鼠的子宫中显著增加，与这些小鼠中局部子宫内膜的促炎环境一致。总之，肥胖与女性 MBL 增加有关。给予高脂肪饮食的小鼠在月经期间子宫内膜修复延迟，并为研究肥胖对月经生理的影响提供了模型。我们的结果表明，肥胖导致月经时局部子宫内膜环境更具炎症性，这可能会延迟子宫内膜修复并增加月经出血量。
