Decidualization regulates the expression of the endometrial chorionic gonadotropin receptor in the primate
Decidualization regulates the expression of the endometrial chorionic gonadotropin receptor in the primate
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DOI：
10.1095/biolreprod.106.051805
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发表时间：
2006-11-01
影响因子：
3.6
通讯作者：
Fazleabas, Asgerally T.
中科院分区：
文献类型：
--
作者：
Cameo, Paula;Szmidt, Maciej;Fazleabas, Asgerally T.
绒毛膜促性腺激素（CG）通过直接调节狒狒子宫内膜间质细胞和上皮细胞的功能，在建立接受性子宫内膜中起重要作用。本研究的重点是表征CG受体（LHCGR，也称为CG-R）表达在月经周期和早期妊娠，特别是在蜕膜化过程中的变化。LHCGR通过使用针对细胞外结构域产生的肽特异性抗体来定位。在周期的增殖阶段，任何细胞类型中均不存在免疫染色。相反，在分泌期，管腔和腺上皮细胞染色阳性。间质染色仅限于螺旋动脉（SA）周围的细胞和基底层。在妊娠第18 - 25天和CG输注后，这种基质染色模式在着床部位持续存在。然而，随着妊娠的进展（第40至60天），基质细胞中LHCGR的染色显着减少。这些数据证实了非同位素原位杂交。为了确认LHCGR的丢失是否与蜕膜反应相关，将基质成纤维细胞在体外蜕膜化，并通过Western印迹分析培养3、6和12天后获得的细胞裂解物。LHCGR蛋白随着体外蜕膜化的发生而下降，证实了体内结果。此外，CG的蜕膜细胞导致在reinduction的LHCGR在dbcAMP的情况下。我们建议CG通过其R作用于基质细胞调节SA，为妊娠和滋养层浸润做准备。随着妊娠的进展，通过迁移血管内滋养细胞和随后的蜕膜化进一步修饰SA导致LHCGR的下调。LHCGR表达的这种抑制也与外周循环中可测量的CG的减少相一致。
Chorionic gonadotropin (CG) plays an important role in establishing a receptive endometrium by directly modulating the function of both endometrial stromal and epithelial cells in the baboon. The focus of this study was to characterize changes in CG receptor (LHCGR, also known as CG-R) expression during the menstrual cycle and early pregnancy, particularly during decidualization. LHCGR was localized by using a peptide-specific antibody generated against the extracellular domain. Immunostaining was absent in any of the cell types during the proliferative phase of the cycle. In contrast, during the secretory phase, both luminal and glandular epithelial cells stained positively. Stromal staining was confined to the cells around spiral arteries (SAs) and in the basalis layer. This stromal staining pattern persisted at the implantation site between Days 18 and 25 of pregnancy and after CG infusion. However, as pregnancy progressed (Days 40 to 60), staining for LHCGR was dramatically decreased in the stromal cells. These data were confirmed by nonisotopic in situ hybridization. To confirm whether the loss of LHCGR was associated with a decidual response, stromal fibroblasts were decidualized in vitro, and cell lysates obtained after 3, 6, and 12 days of culture were analyzed by Western blotting. LHCGR protein decreased with the onset of decidualization in vitro, confirming the in vivo results. Addition of CG to decidualized cells resulted in the reinduction of LHCGR in the absence of dbcAMP. We propose that CG acting via its R on stromal cells modulates SA in preparation for pregnancy and trophoblast invasion. As pregnancy progresses, further modification of SA by migrating endovascular trophoblasts and subsequent decidualization results in the downregulation of LHCGR. This inhibition of LHCGR expression also coincides with the decrease of measurable CG in peripheral circulation.