Abstract
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.
Highlights
Major functions of the uterus include receiving the embryo, sheltering the fetus during pregnancy, and delivering the newborn at term
These results suggest that G-protein coupled receptor 64 (GPR64) may have an important role for implantation and decidualization during early pregnancy
Our results showed that Gpr[64] mRNA expression was significantly increased in the uteri of mice treated with P4 as compared with vehicle and E2 (Fig. 2a)
Summary
Major functions of the uterus include receiving the embryo, sheltering the fetus during pregnancy, and delivering the newborn at term. The uterus undergoes dynamic molecular and morphological changes to allow for embryo implantation and development These changes of uterine components are tightly regulated by two ovarian steroid hormones, estrogen (E2) and progesterone (P4)[1]. Endometrial stromal cells undergoing decidualization become plumper, acquire a secretory epithelioid-like morphology, and secrete a variety of factors, including prolactin (PRL) and insulin-like growth factor binding protein 1 (IGFBP1)[10]. Decidualization process occurs in stromal cells surrounding the spiral arties approximately 10 days after the postovulatory rise in ovarian P4 level, indicating that the expression of the decidua-specific genes is under the direct control of activated PGR. The identification of P4-PGR regulated genes is crucial in understanding the causes of impairments in fertility
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