Stoikos Chelsea J, Harrison Craig A, Salamonsen Lois A, Dimitriadis Evdokia
Prince Henry's Institute of Medical Research, PO Box 5152, Clayton, Victoria 3168, Australia.
Hum Reprod. 2008 Jun;23(6):1447-56. doi: 10.1093/humrep/den110. Epub 2008 Apr 23.
Successful blastocyst implantation requires the differentiation of human endometrial stromal cells (HESC), a process known as decidualization. Activin A, a transforming growth factor beta (TGFbeta) superfamily member, enhances HESC decidualization and localizes to decidual cells in human endometrium. Other TGFbeta superfamily members, including BMP2, BMP4, BMP7, GDF5, GDF8, GDF11, TGFbetas and Nodal, may also play a role during decidualization. This study aimed to identify these TGFbeta family members in human endometrium, and to determine whether they are involved in human decidualization.
Protein localization of TGFbeta family members was examined in secretory phase human endometrium and first trimester decidua by immunohistochemistry. mRNA expression was examined in HESC. Activin inhibitors (Activin-M108A/SB431542) with differing specificities for the other TGFbeta members under consideration were applied during HESC decidualization in vitro. The secretion levels of potential TGFbeta superfamily members were measured during decidualization, and recombinant proteins added to examine their effect.
This study has identified BMP2, BMP4, BMP7, GDF5, GDF8 and GDF11 but not Nodal in secretory phase human endometrium, but only BMP2, GDF5 and TGFbeta1 protein were detected in decidual cells. All ligands except Nodal were expressed by cultured HESC. Both inhibitors significantly reduced decidualization validating the role of activin, but potentially also other TGFbeta members, during decidualization. BMP2 and TGFbeta1 secretion increased during HESC decidualisation and exogenous administration of these proteins significantly enhanced decidualization in vitro.
Like activin, BMP2 and TGFbeta1 are likely to be involved in HESC decidualization. This is the first study to identify and localize BMP4, BMP7, GDF5, GDF8 and GDF11 in secretory phase human endometrium. Understanding the factors critical for the implantation process is needed for improving fertility and pregnancy outcomes.
成功的囊胚着床需要人子宫内膜基质细胞（HESC）的分化，这一过程称为蜕膜化。激活素A是转化生长因子β（TGFβ）超家族成员，可增强HESC蜕膜化，并定位于人子宫内膜的蜕膜细胞。其他TGFβ超家族成员，包括骨形态发生蛋白2（BMP2）、骨形态发生蛋白4（BMP4）、骨形态发生蛋白7（BMP7）、生长分化因子5（GDF5）、生长分化因子8（GDF8）、生长分化因子11（GDF11）、TGFβs和Nodal，在蜕膜化过程中可能也发挥作用。本研究旨在鉴定人子宫内膜中的这些TGFβ家族成员，并确定它们是否参与人蜕膜化过程。
通过免疫组织化学检测TGFβ家族成员在分泌期人子宫内膜和孕早期蜕膜中的蛋白定位。检测HESC中的mRNA表达。在体外HESC蜕膜化过程中应用对其他所考虑的TGFβ成员具有不同特异性的激活素抑制剂（激活素-M108A/ SB431542）。在蜕膜化过程中测量潜在TGFβ超家族成员的分泌水平，并添加重组蛋白以检测其作用。
本研究在分泌期人子宫内膜中鉴定出BMP2、BMP4、BMP7、GDF5、GDF8和GDF11，但未鉴定出Nodal，而在蜕膜细胞中仅检测到BMP2、GDF5和TGFβ1蛋白。除Nodal外的所有配体均由培养的HESC表达。两种抑制剂均显著降低蜕膜化，证实了激活素以及可能其他TGFβ成员在蜕膜化过程中的作用。在HESC蜕膜化过程中BMP2和TGFβ1分泌增加，外源性给予这些蛋白可显著增强体外蜕膜化。
与激活素一样，BMP2和TGFβ1可能参与HESC蜕膜化。这是首次在分泌期人子宫内膜中鉴定并定位BMP4、BMP7、GDF5、GDF8和GDF11。改善生育能力和妊娠结局需要了解着床过程中的关键因素。
Zotero 插件
