Pregnancy-associated plasma protein A in human ovarian follicles and its association with intrafollicular hormone levels
Pregnancy-associated plasma protein A in human ovarian follicles and its association with intrafollicular hormone levels
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DOI：
10.1016/j.fertnstert.2015.07.1152
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发表时间：
2015-11-01
影响因子：
6.7
通讯作者：
Andersen, Claus Yding
中科院分区：
文献类型：
--
作者：
Botkjaer, Jane Alro;Jeppesen, Janni Vikkelso;Andersen, Claus Yding
目的：评价卵泡液（FF）中妊娠相关血浆蛋白A（PAPP-A）水平与卵泡内激素水平的关系。此外，研究了不同直径的人卵泡的PAPP-A、抗苗勒管激素（AMH）和芳香化酶的免疫染色，并评估了FF中PAPP-A的生物活性。设计：实验室调查。设置：大学医院。患者：共43名妇女，共80个样本，从三个不同大小组的窦卵泡收集前后LH激增。干预（（s）：类固醇、PAPP-A和AMH的ELISA测量，不同直径卵泡上PAPP-A、AMH和芳香化酶的免疫组织化学，以及PAPP-A对胰岛素样生长因子（IGF）结合蛋白4（IGFBP-4）的蛋白水解活性。FF中PAPP-A水平与测量的卵巢激素、FF中PAPP-A活性、PAPP-A定位、AMH、结果：FF中PAPP-A水平与所有测量的激素之间存在高度显著的相关性，与E-2和P呈正相关，而AMH、T和A呈强负相关。在人FF中检测到PAPP-A对IGFBP-4的蛋白水解活性。PAPP-A免疫染色从主要存在于小窦卵泡的卵泡膜细胞转变为表达于排卵前卵泡的颗粒细胞（GC）。相反，AMH的表达随着卵泡直径的增加而减少。结论：PAPP-A特异性地参与了人有腔卵泡甾体激素合成的调控。局部调节IGF-II活性可能是PAPP-A发挥这一功能的机制，并强调了卵泡发育过程中IGF信号的重要性。(C)2015年，美国生殖医学会（American Society for Reproductive Medicine）
Objective: To evaluate follicular fluid (FF) levels of pregnancy-associated plasma protein A (PAPP-A) in relation to levels of intrafollicular hormones. Furthermore, immunostaining of human follicles of varying diameters was studied for PAPP-A, antimullerian hormone (AMH), and aromatase, and the biological activity of PAPP-A in FF was evaluated.Design: Laboratory investigation.Setting: University hospital.Patient(s): A total of 43 women with a total of 80 samples were obtained from three different size-groups of antral follicles collected before and after the LH surge.Intervention(s): ELISA measurement of steroids, PAPP-A, and AMH, immunohistochemistry of PAPP-A, AMH, and aromatase on follicles of different diameter, and proteolytic activity of PAPP-A toward insulin-like growth factor (IGF)-binding protein 4 (IGFBP-4).Main Outcome Measure(s): Association between FF levels of PAPP-A and measured ovarian hormones, PAPP-A activity in FF, localization of PAPP-A, AMH, and aromatase in antral follicles.Result(s): A highly significant association between FF levels of PAPP-A and all measured hormones were obtained with positive associations toward E-2 and P, whereas AMH, T, and A showed strong negative associations. PAPP-A proteolytic activity toward IGFBP-4 was detected in human FF. PAPP-A immunostaining shifted from being primarily present in theca cells of small antral follicles to being expressed in granulosa cells (GCs) of preovulatory follicles. In contrast, AMH expression became reduced with increasing follicular diameter. Aromatase expression was highly specifically localized to GCs of preovulatory follicles.Conclusion(s): The results suggest that PAPP-A is specifically involved in the regulation of steroidogenesis in human antral follicles. Local regulation of IGF-II activity may represent a mechanism by which PAPP-A exerts this function and highlights the importance of IGF signaling during follicular development. (C) 2015 by American Society for Reproductive Medicine.