Instituto de Biopatología y Medicina Regenerativa, Centro de Investigación Biomédica, Universidad de Granada, Armilla, Granada, Spain.
Servicio de Obstetricia y Ginecología, Hospital Universitario Virgen de las Nieves, Granada, Spain.
Reproduction. 2020 Jul;160(1):83-91. doi: 10.1530/REP-19-0465.
Endometrial stromal cells (EnSCs) and decidual stromal cells (DSCs) originate from fibroblastic precursors located around the vessels of the human nonpregnant endometrium and the pregnant endometrium (decidua), respectively. Under the effect of ovarian or pregnancy hormones, these precursors differentiate (decidualize), changing their morphology and secreting factors that appear to be essential for the normal development of pregnancy. However, the different physiological context - that is, non-pregnancy vs pregnancy - of those precursors (preEnSCs, preDSCs) might affect their phenotype and functions. In the present study, we established preEnSC and preDSC lines and compared the antigen phenotype and responses to decidualization factors in these two types of stromal cell line. Analyses with flow cytometry showed that preEnSCs and preDSCs exhibited a similar antigen phenotype compatible with that of bone marrow mesenchymal stem/stromal cells. The response to decidualization in cultures with progesterone and cAMP was evaluated by analyzing changes in cell morphology by microscopy, prolactin and IL-15 secretion by enzyme immunoassay and the induction of apoptosis by flow cytometry. In all four analyses, preDSCs showed a significantly higher response than preEnSCs. The expression of progesterone receptor (PR), protein kinase A (PKA) and FOXO1 was studied with Western blotting. Both types of cells showed similar levels of PR and PKA, but the increase in PKA RI subunit expression in response to decidualization was again significantly greater in preDSCs. We conclude that preEnSCs and preDSCs are equivalent cells but differ in their ability to decidualize. Functional differences between them probably derive from factors in their different milieus.
子宫内膜基质细胞(EnSCs)和蜕膜基质细胞(DSCs)分别来源于人未怀孕子宫内膜和怀孕子宫内膜(蜕膜)血管周围的成纤维前体细胞。在卵巢或妊娠激素的作用下,这些前体细胞(preEnSCs、preDSCs)分化(蜕膜化),改变其形态并分泌因子,这些因子似乎对妊娠的正常发育至关重要。然而,这些前体细胞所处的不同生理环境——即非妊娠与妊娠——可能会影响它们的表型和功能。在本研究中,我们建立了 preEnSC 和 preDSC 系,并比较了这两种基质细胞系的抗原表型和对蜕膜化因子的反应。流式细胞术分析表明,preEnSCs 和 preDSCs 表现出与骨髓间充质干细胞相似的抗原表型。通过显微镜观察细胞形态变化、酶联免疫吸附法检测催乳素和 IL-15 分泌以及流式细胞术检测细胞凋亡,评估孕激素和 cAMP 培养物中的蜕膜化反应。在所有四项分析中,preDSCs 的反应均明显高于 preEnSCs。通过 Western blot 研究了孕激素受体(PR)、蛋白激酶 A(PKA)和 FOXO1 的表达。两种类型的细胞均表现出相似水平的 PR 和 PKA,但 preDSCs 中 PKA RI 亚基表达在蜕膜化反应中的增加更为显著。我们得出结论,preEnSCs 和 preDSCs 是等效的细胞,但在蜕膜化能力上存在差异。它们之间的功能差异可能源于其不同微环境中的因素。