Cell Biology Unit, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.
FASEB J. 2013 Sep;27(9):3711-9. doi: 10.1096/fj.13-232074. Epub 2013 May 31.
Menstrual endometrial breakdown induced by estradiol and progesterone withdrawal is regularly attributed to vasospasm of spiral arteries causing ischemia and hypoxia. We investigated whether hypoxia actually occurred in an in vivo model of menstruation. Three complementary approaches were used to look for signs of hypoxia in fragments of human functionalis xenografted to ovariectomized immunodeficient mice bearing pellets-releasing estradiol and progesterone, and then deprived of ovarian steroids. Hormone withdrawal 21 d after grafting induced menstrual breakdown and MMP expression within 4 d. Local partial oxygen pressure (pO2) was measured by electron paramagnetic resonance using implanted lithium phtalocyanine crystals. In mice with hormone maintenance until sacrifice, pO2 was low one week after grafting (14.8±3.4 mmHg) but increased twofold from the second week when tissue was largely revascularized. After 3 wk, pO2 was not modified by hormone withdrawal but was slightly increased on hormone reimpregnation 4 d after removal (34.7±6.1 mmHg) by comparison with hormone maintenance (27.1±8.6 mmHg). These results were confirmed using fluorescence quenching-based OxyLite measurements. In a further search for signs of hypoxia, we did not find significant HIF1-α immunostaining, nor pimonidazole adducts after hormone withdrawal. We conclude that hypoxia is not needed to trigger menstrual-like tissue breakdown or repair in human endometrial xenograft.
雌激素和孕激素撤退引起的月经子宫内膜破裂通常归因于螺旋动脉的血管痉挛导致缺血和缺氧。我们研究了在月经的体内模型中是否实际上发生了缺氧。使用三种互补的方法来寻找在移植到卵巢切除的免疫缺陷小鼠的人类功能性移植物中缺氧的迹象，这些小鼠携带释放雌激素和孕激素的丸剂，然后被剥夺卵巢类固醇。移植后 21 天撤去激素会导致月经破裂和 MMP 表达在 4 天内发生。通过使用植入的锂酞菁晶体，通过电子顺磁共振测量局部局部氧分压（pO2）。在激素维持至处死的小鼠中，移植后一周的 pO2 较低（14.8±3.4 mmHg），但当组织大部分再血管化时，从第二周开始增加一倍。3 周后，激素撤退不会改变 pO2，但在去除后 4 天重新注入激素时会略有增加（34.7±6.1 mmHg），与激素维持相比（27.1±8.6 mmHg）。这些结果使用荧光猝灭基 OxyLite 测量得到了证实。在进一步寻找缺氧迹象的过程中，我们在激素撤退后没有发现明显的 HIF1-α免疫染色，也没有发现 pimonidazole 加合物。我们得出的结论是，缺氧不是触发人类子宫内膜移植物类似月经的组织破裂或修复所必需的。
