Teasley Hanna E, Chang Hye Jin, Kim Tae Hoon, Ku Bon Jeong, Jeong Jae-Wook
Department of Obstetrics, Gynecology & Reproductive Biology, Michigan State University, College of Human Medicine, Grand Rapids, MI 49503, USA; Department of Biology, Kalamazoo College, Kalamazoo, MI, USA.
Department of Obstetrics, Gynecology & Reproductive Biology, Michigan State University, College of Human Medicine, Grand Rapids, MI 49503, USA; Health Promotion Center, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Biochem Biophys Res Commun. 2018 Jan 22;495(4):2553-2558. doi: 10.1016/j.bbrc.2017.12.154. Epub 2017 Dec 28.
The ovarian steroid hormones, estrogen (E2) and progesterone (P4), are essential regulators of uterine functions necessary for development, embryo implantation, and normal pregnancy. ARID1A plays an important role in steroid hormone signaling in endometrial function and pregnancy. In previous studies, using high density DNA microarray analysis, we identified phosphatidylinositol-3-kinase interacting protein 1 (Pik3ip1) as one of the genes up-regulated by ARID1A. In the present study, we performed real-time qPCR and immunohistochemistry analysis to investigate the regulation of PIK3IP1 by ARID1A and determine expression patterns of PIK3IP1 in the uterus during early pregnancy. The expression of PIK3IP1 was strong at the uterine epithelial and stromal cells of the control mice. However, expression of PIK3IP1 was remarkably reduced in the PgrArid1a mice and progesterone receptor knock-out (PRKO) mice. During early pregnancy, PIK3IP1 expression was strong at day 2.5 of gestation (GD 2.5) and then slightly decreased at GD 3.5 at the epithelium and stroma. After implantation, PIK3IP1 expression was detected at the secondary decidualization zone. To determine the ovarian steroid hormone regulation of PIK3IP1, we examined the expression of PIK3IP1 in ovariectomized control, PgrArid1a, and PRKO mice treated with P4 or E2. P4 treatment increased the PIK3IP1 expression at the luminal and glandular epithelium of control mice. However, the PIK3IP1 induction was decreased in both the PgrArid1a and PRKO mice, compared to controls. Our results identified PIK3IP1 as a novel target of ARID1A and PGR in the murine uterus.
卵巢甾体激素，雌激素（E2）和孕酮（P4），是子宫功能的重要调节因子，对发育、胚胎着床和正常妊娠至关重要。ARID1A在子宫内膜功能和妊娠的甾体激素信号传导中起重要作用。在先前的研究中，我们使用高密度DNA微阵列分析，将磷脂酰肌醇-3-激酶相互作用蛋白1（Pik3ip1）鉴定为受ARID1A上调的基因之一。在本研究中，我们进行了实时定量PCR和免疫组织化学分析，以研究ARID1A对PIK3IP1的调节作用，并确定妊娠早期子宫中PIK3IP1的表达模式。PIK3IP1在对照小鼠的子宫上皮和基质细胞中表达强烈。然而，PIK3IP1在PgrArid1a小鼠和孕酮受体敲除（PRKO）小鼠中的表达显著降低。在妊娠早期，PIK3IP1在妊娠第2.5天（GD 2.5）时表达强烈，然后在GD 3.5时在上皮和基质中略有下降。着床后，在次级蜕膜化区域检测到PIK3IP1表达。为了确定卵巢甾体激素对PIK3IP1的调节作用，我们检测了用P4或E2处理的去卵巢对照、PgrArid1a和PRKO小鼠中PIK3IP1的表达。P4处理增加了对照小鼠腔上皮和腺上皮中PIK3IP1的表达。然而，与对照相比，PgrArid1a和PRKO小鼠中PIK3IP1的诱导均降低。我们的结果确定PIK3IP在小鼠子宫中是ARID1A和PGR 的新靶点。
