Yang Qianlan, Wang Wangsheng, Liu Chao, Wang Yu, Sun Kang
Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, PR China; Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, PR China.
Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, PR China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, PR China.
Placenta. 2016 Oct;46:63-71. doi: 10.1016/j.placenta.2016.08.079. Epub 2016 Aug 28.
Glucocorticoids are engaged in a number of actions at the feto-maternal interface for the establishment of early pregnancy. However, excessive glucocorticoids can be deleterious to fetal development. Therefore, compartmentalized distribution of 11β-hydroxysteroid dehydrogenase 1 and 2 (11β-HSD1 and 2), which regenerates and inactivates cortisol respectively, would ensure an optimal cortisol concentration at the feto-maternal interface for the establishment of early gestation. However, the distribution pattern of 11β-HSD1 and 2 at the feto-maternal interface in early human pregnancy is not clearly defined. Here we showed that 11β-HSD1 distributed extensively on the maternal side including decidual stromal cells and epithelial cells but scarcely on the fetal side except for localization in the fetal blood vessels of the chorionic villi. In contrast, 11β-HSD2 was abundantly localized in syncytial layer of the chorionic villi and the decidual epithelium. In primary cultures, cortisol upregulated not only 11β-HSD1 expression in decidual stromal cells but also 11β-HSD2 expression in villous trophoblasts of early pregnancy. Further studies revealed that cortisol inhibited the expression of interleukin-1β and 6 in decidual stromal cells and villous trophoblasts, and stimulated expression of human chorionic gonadotropin in villous trophoblasts. Collectively, this study has revealed a compartmentalized distribution pattern of 11β-HSD 1 and 2 at the feto-maternal interface, both of which can be upregulated by glucocorticoids, suggesting that a coordinated interaction between 11β-HSD 1 and 2 may exist to ensure an optimal cortisol concentration at discrete locations at the feto-maternal interface for the establishment of early pregnancy.
糖皮质激素在母胎界面参与多种建立早期妊娠的活动。然而，过量的糖皮质激素可能对胎儿发育有害。因此，11β-羟基类固醇脱氢酶1和2（11β-HSD1和2）分别使皮质醇再生和失活的分区分布，将确保在母胎界面有最佳的皮质醇浓度以建立早期妊娠。然而，在人类妊娠早期母胎界面11β-HSD1和2的分布模式尚不清楚。在此我们表明，11β-HSD1广泛分布于母体一侧，包括蜕膜基质细胞和上皮细胞，但在胎儿一侧除了在绒毛膜绒毛的胎儿血管中有定位外几乎没有分布。相反，11β-HSD2大量定位于绒毛膜绒毛的合体层和蜕膜上皮。在原代培养中，皮质醇不仅上调蜕膜基质细胞中11β-HSD1的表达，还上调早孕绒毛滋养层细胞中11β-HSD2的表达。进一步研究表明，皮质醇抑制蜕膜基质细胞和绒毛滋养层细胞中白细胞介素-1β和6的表达，并刺激绒毛滋养层细胞中人绒毛膜促性腺激素的表达。总体而言，本研究揭示了11β-HSD 1和2在母胎界面的分区分布模式，二者均可被糖皮质激素上调，提示11β-HSD 1和2之间可能存在协同相互作用，以确保在母胎界面的离散位置有最佳的皮质醇浓度来建立早期妊娠。
