Deparment of Obstetrics and Gynecology & Reproductive Biology, Michigan State University, College of Human Medicine, Grand Rapid, MI, 49503, United States.
Research Institutes of Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
Sci Rep. 2017 Jul 10;7(1):5021. doi: 10.1038/s41598-017-05165-8.
Although GPR64 has an important role for male fertility, its physiological roles in the female reproductive system are still unknown. In the present study, immunohistochemical analysis reveals a spatiotemporal expression of GPR64 in the uterus during early pregnancy. Observation of remarkable induction of GPR64 expression in uterine decidual cells points to its potential physiological significance on decidualization. The decidualization of uterine stromal cells is a key event in implantation. Progesterone (P4) signaling is crucial for the decidualization of the endometrial stromal cells for successful pregnancy. Therefore, we examined ovarian steroid hormone regulation of GPR64 expression in the murine uterus. P4 induced GPR64 expression in the epithelial and stromal cells of the uterus in ovariectomized wild-type mice, but not in PRKO mice. ChIP analysis confirmed that PGR proteins were recruited on progesterone response element of Gpr64 gene in the uteri of wild-type mice treated with P4. Furthermore, the expression of GPR64 was increased in human endometrial stromal cells (hESCs) during in vitro decidualization. Interestingly, small interfering RNA (siRNA)-mediated knockdown of GPR64 in hESCs remarkably reduced decidualization. These results suggest that Gpr64 has a crucial role in the decidualization of endometrial stromal cells.
虽然 GPR64 对男性生育力有重要作用，但它在女性生殖系统中的生理作用尚不清楚。在本研究中，免疫组织化学分析揭示了 GPR64 在妊娠早期子宫中的时空表达。观察到 GPR64 在子宫蜕膜细胞中的表达显著诱导，表明其在蜕膜化中的潜在生理意义。子宫基质细胞的蜕膜化是着床的关键事件。孕激素（P4）信号对于子宫内膜基质细胞的蜕膜化对于成功妊娠至关重要。因此，我们研究了卵巢甾体激素对小鼠子宫中 GPR64 表达的调节。P4 在去卵巢野生型小鼠的子宫上皮和基质细胞中诱导 GPR64 表达，但在 PRKO 小鼠中没有。ChIP 分析证实，在接受 P4 处理的野生型小鼠的子宫中，PGR 蛋白被募集到 Gpr64 基因的孕激素反应元件上。此外，GPR64 在体外蜕膜化过程中在人子宫内膜基质细胞（hESCs）中的表达增加。有趣的是，hESCs 中的 GPR64 的小干扰 RNA（siRNA）介导的敲低显著降低了蜕膜化。这些结果表明 Gpr64 在子宫内膜基质细胞的蜕膜化中具有重要作用。
