The Window of Implantation Is Closed by Estrogen via Insulin-Like Growth Factor 1 Pathway

• Published in: Journal of reproduction & infertility Vol. 18; no. 2; pp. 231 - 241
• Main Authors: Kobayashi, Ryosuke, Terakawa, Jumpei, Omatsu, Tsutomu, Hengjan, Yupadee, Mizutani, Tetsuya, Ohmori, Yasushige, Hondo, Eiichi
• Format: Journal Article
• Language: English
• Published: Iran Office for Scientific Journals 01.04.2017; Avicenna Research Institute
• Subjects: Cell growth; Cell proliferation; Endometrium; Epithelium; Estrogens; Gene expression; Implantation; Injection; Insulin; Insulin-like growth factor I; Insulin-like growth factors; Leukocytes (neutrophilic); Medroxyprogesterone acetate; Mice; Original; Ovariectomy; Pregnancy; Progesterone; Ribonucleic acid; RNA; Rodents; Surgical implants; Transplants & implants; Uterus; Windows (computer programs); Embryo implantation; Mouse; Insulin-like growth factor 1; Estrogen
• ISSN: 2228-5482; 2251-676X

The opening and closing of the implantation window is important for successful pregnancy in eutherians. The recent study demonstrated that the window of uterine receptivity was prepared by the sole action of progesterone in mice, but the mechanism to close the window remained to be elucidated. The pregnant mice were ovariectomized on the evening on the third day of pregnancy with a single injection of medroxyprogesterone acetate to induce delayed implantation (DI). Several treatments were applied to DI mice. The uterine receptivity after treatment was assessed by examining cell proliferation in the uterine luminal epithelium (LE). The gene expressions in the endometrium were investigated by RNA-seq. The p<0.05 was considered significant. Cell proliferation in the LE ceased only when the window of implantation was open. Estrogen (E2) stimulated cell proliferation in the LE rendered the uterus refractory. The high throughput gene expression analysis by RNA-Seq showed that the insulin-like growth factor 1 (IGF1) pathway was the candidate to close the implantation window under E2. administration of IGF1 to delayed implantation mice resulted in proliferation in the LE cells. This study demonstrated that the window of uterine receptivity was closed by E2, which was mediated by the IGF1 pathway.