Yan Xingyu, Rong Miaomiao, Zhou Qianhui, Zhang Cong
Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200135, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China; Fujian Provincial Key Laboratory of Reproductive Health Research, Medical College of Xiamen University, Xiamen, Fujian, 361102, China.
Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan, Shandong, 250014, China.
Mol Cell Endocrinol. 2022 Oct 1;556:111741. doi: 10.1016/j.mce.2022.111741. Epub 2022 Aug 4.
Preeclampsia (PE) is a syndrome that occurs during pregnancy and affects more than 8 million mother-infant pairs each year. Most previous studies on the pathogenesis of PE have focused on the placenta. However, decidualization is the basis for placentation and subsequent development. The CRL4 (Cullin 4-RING E3 ubiquitin ligase) complex ubiquitinates and degrades substrates, while DCAF13 (DDB1 and CUL4-associated factor 13) is a component and substrate receptor of this complex, which recognizes and recruits the complex different substrates. DCAF13 plays a major role in the maintenance of follicles and the development of oocytes. However, its role in subsequent pregnancies remains unclear. In the present study, we first investigated DCAF13 levels in the decidua of PE patients and found that it is significantly lower than that of normal pregnant women. Second, we found that DCAF13 expression increases during decidualization, and reducing expression of DCAF13 by siRNA prevents decidualization. Third, in vivo experiments in mice further revealed that Dcaf13 expression increases with decidualization. Finally, we generated and found that uteri of pseudopregnant conditional Dcaf13 knockout mice fails to undergo decidualization. Therefore, we propose that DCAF13 plays a key role in decidualization. Abnormal expression of DCAF13 affects the decidualization process, which is likely involved in the occurrence and development of PE.
子痫前期（PE）是一种在孕期出现的综合征，每年影响超过800万母婴。以往大多数关于PE发病机制的研究都集中在胎盘。然而，蜕膜化是胎盘形成及后续发育的基础。CRL4（Cullin 4 - RING E3泛素连接酶）复合物使底物泛素化并降解，而DCAF13（DDB1和CUL4相关因子13）是该复合物的一个组成部分和底物受体，可识别并募集该复合物的不同底物。DCAF13在卵泡维持和卵母细胞发育中起主要作用。然而，其在后续妊娠中的作用仍不清楚。在本研究中，我们首先调查了PE患者蜕膜中DCAF13的水平，发现其显著低于正常孕妇。其次，我们发现DCAF13的表达在蜕膜化过程中增加，通过小干扰RNA降低DCAF13的表达可阻止蜕膜化。第三，小鼠体内实验进一步表明Dcaf13的表达随蜕膜化增加。最后，我们构建并发现假孕条件性Dcaf13基因敲除小鼠的子宫未能发生蜕膜化。因此，我们提出DCAF13在蜕膜化中起关键作用。DCAF13的异常表达影响蜕膜化过程，这可能与PE的发生和发展有关。
