Loss of X Chromosome Inactivation in Androgenetic Complete Hydatidiform Moles With 46, XX Karyotype.
Loss of X Chromosome Inactivation in Androgenetic Complete Hydatidiform Moles With 46, XX Karyotype.
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DOI：
10.1097/pgp.0000000000000697
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发表时间：
2021-07-01
期刊：
影响因子：
--
通讯作者：
Cheng X
中科院分区：
文献类型：
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作者：
Chen X;Ma Y;Wang L;Zhang X;Yu Y;Lü W;Xie X;Cheng X
大多数完整的葡萄胎（CHM）展示了核基因组的雄激素遗传性质。在正常女性胚胎中，2 条 X 染色体之一不活跃。然而，雄激素遗传 CHM 中 X 染色体失活 (XCI) 的状态仍然未知。收集了 71 个具有 46, XX 核型的雄激素 CHM 组织。收集74个正常女性绒毛和74个正常男性绒毛作为对照。通过实时聚合酶链反应检测 XCI 标记（XIST、TSIX 和 XACT）和 X 连锁基因（CDX4）的表达。还检查了其他 XCI 相关基因，包括通过甲基化特异性聚合酶链反应检测人雄激素受体基因 (HUMARA) 的甲基化状态，以及分别通过蛋白质印迹和免疫荧光检测 H3K27me3、USP21 和 Nanog 的表达。此外，收集126个CHM和63个正常女性绒毛样本进行CDX4免疫组化染色。雄激素性 CHM 中 XIST RNA 表达量显着低于正常雌性绒毛，TSIX RNA 表达量显着高于正常雌性绒毛（均 P<0.01）。雄激素性CHMs中CDX4 mRNA表达量较正常男性和正常女性绒毛样本升高（均P<0.01），CDX4蛋白表达量也高于正常女性绒毛样本（P<0.01）。雄激素性CHMs中H3K27me3的表达低于正常雌性绒毛（P<0.01）。发现雄激素 CHM 缺乏 HUMARA 甲基化模式。雄激素性CHMs中Nanog和UPS21蛋白的表达量均高于正常绒毛（均P<0.01）。两条 X 染色体在 46, XX 核型的雄激素 CHM 中都很活跃，USP21-Nanog 途径可能参与此过程中 XCI 的破坏。
Most complete hydatidiform moles (CHMs) showcase an androgenetic nature of the nuclear genome. In the normal female embryo, one of the 2 X chromosomes is inactive. However, the status of X chromosome inactivation (XCI) in androgenetic CHMs remains unknown. Seventy-one androgenetic CHM tissues with the 46, XX karyotype were collected. Seventy-four normal female villi and 74 normal male villi were collected as controls. The expression of XCI markers (XIST, TSIX, and XACT) and an X-linked gene (CDX4) was detected by real-time polymerase chain reaction. Other XCI-associated genes were also examined, including the methylation status of the human androgen receptor gene (HUMARA) by methylation-specific polymerase chain reaction), and the expression of H3K27me3, USP21, and Nanog by Western blot and immunofluorescence, respectively. In addition, 126 CHMs and 63 normal female villous samples were collected for CDX4 immunohistochemical staining. The expression of XIST RNA was significantly lower, and TSIX RNA expression was significantly higher in androgenetic CHMs than that in normal female villi (both P<0.01). The expression of CDX4 mRNA in androgenetic CHMs was elevated compared with that in normal male and normal female villous samples (both P<0.01), and CDX4 protein expression was also higher than that in normal female villous samples (P<0.01). The expression of H3K27me3 was lower in androgenetic CHMs compared with that in normal female villi(P<0.01). The methylation pattern of HUMARA was found lacking in androgenetic CHMs. The expression of Nanog and UPS21 protein in androgenetic CHMs was higher than that in normal villi (both P<0.01). Both X chromosomes are active in androgenetic CHMs with the 46, XX karyotype, and the USP21-Nanog pathway may be involved in the disruption of XCI during this process.