Endometrial Physiology

我们最近研究了子宫内膜异位症患者的子宫内膜在月经周期的着床期是否异常。 我们采用前瞻性观察性研究设计，评估了植入生物标志物，糖溶蛋白A（GdA），骨桥蛋白（OPN），溶血磷脂酸受体3（LPA 3）和HOXA 10在子宫内膜异位症和非子宫内膜异位症妇女在位子宫内膜中的表达。24名子宫内膜异位症患者和23名年龄相仿的健康志愿者在分泌期进行子宫内膜活检，并对GdA、OPN、LPA 3和HOXA 10的免疫组织化学染色强度和定位进行评价。 周期第22天后患者子宫内膜GdA表达显著降低。子宫内膜异位症患者的子宫内膜在分泌晚期OPN表达减少，在分泌中期和分泌晚期LPA 3和HOXA 10表达减少。这四种着床生物标志物的表达降低可能表明子宫内膜异位症患者的子宫内膜容受性受损，为即使在盆腔植入物很少的女性中观察到的生育力低下提供了一种解释。由于这些标记物中有许多是孕酮依赖性的，这些发现表明在这一人群中子宫内膜孕酮作用降低的可能性。 我们还研究了SPRM CDB-2914对黄体早期子宫内膜的影响。五十六例周期规律的妇女在排卵后和LH峰2天内接受单剂量CDB-2914（10、50或100 mg）或安慰剂。4 - 6天后，经阴道超声扫描测量子宫内膜厚度，并获得子宫内膜活检标本。通过厚度和P依赖性标记物的免疫组织化学分析评估子宫内膜;进行安全性实验室检查，并获得E（2）和P水平。CDB-2914引起子宫内膜厚度的显著剂量依赖性降低、腺P受体的增加和外周淋巴结地址素的减少。雌二醇和P水平和月经周期时间没有改变。未观察到不良反应。在激素水平和周期长度没有变化的情况下，子宫内膜厚度和P-依赖性着床标志物的改变表明CDB-2914可能具有避孕特性。

We recently studied whether the endometrium of women with endometriosis might be abnormal during the implantation phase of the menstrual cycle. We evaluated the expression of biomarkers of implantation, glycodelin A (GdA), osteopontin (OPN), lysophosphatidic acid receptor 3 (LPA3), and HOXA10, in eutopic endometrium of women with and without endometriosis using a prospective observational study design. Twenty-four women with endometriosis and 23 healthy volunteers of similar age underwent an endometrial biopsy in the secretory phase and the immunohistochemical staining intensity and localization of GdA, OPN, LPA3, and HOXA10 was evaluated. Endometrial GdA expression was significantly reduced in patients after cycle day 22. The endometrium from women with endometriosis also showed decreased expression of OPN in the late secretory phase and LPA3 and HOXA10 expression in the midsecretory and late secretory phases. The decreased expression of these four biomarkers of implantation may indicate impaired endometrial receptivity in patients with endometriosis, providing one explanation for the subfertility observed even in women with few pelvic implants. Because many of these markers are progesterone dependent, these findings suggest the possibility of reduced endometrial progesterone action in this population. We have also examined the effect of the SPRM CDB-2914 on endometrium in the early luteal phase. Fifty-six women with regular cycles received a single dose of CDB-2914 (10, 50, or 100 mg) or placebo given after ovulation and within 2 days of the LH surge. Four to 6 days later, a transvaginal ultrasound scan measured endometrial thickness, and an endometrial biopsy specimen was obtained. The endometrium was evaluated by thickness and by immunohistochemical analysis for P-dependent markers; safety laboratory tests were performed, and E(2) and P levels were obtained. CDB-2914 caused a significant dose-dependent decrease in endometrial thickness, an increase in glandular P receptors, and a decrease in peripheral node addressins. Estradiol and P levels and menstrual cycle timing were not altered. No adverse effects were observed. The alteration in endometrial thickness and P-dependent markers of implantation in the absence of changes in hormone levels and cycle length suggests that CDB-2914 may have contraceptive properties.