Kobayashi Ryosuke, Terakawa Jumpei, Omatsu Tsutomu, Hengjan Yupadee, Mizutani Tetsuya, Ohmori Yasushige, Hondo Eiichi
Laboratory of Animal Morphology, Division of Biofunctional Development, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
Division of Transgenic Animal Science, Advanced Science Research Center, Kanazawa University, Kanazawa, Japan.
J Reprod Infertil. 2017 Apr-Jun;18(2):231-241.
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.
着床窗口的开启和关闭对于真兽类动物成功妊娠至关重要。最近的研究表明，在小鼠中，子宫容受性窗口仅由孕酮的单一作用所准备，但关闭该窗口的机制仍有待阐明。
在妊娠第三天晚上对妊娠小鼠进行卵巢切除术，并单次注射醋酸甲羟孕酮以诱导延迟着床（DI）。对DI小鼠进行了几种处理。通过检查子宫腔上皮（LE）中的细胞增殖来评估处理后的子宫容受性。通过RNA测序研究子宫内膜中的基因表达。p<0.05被认为具有统计学意义。
仅在着床窗口开放时，LE中的细胞增殖才会停止。雌激素（E2）刺激LE中的细胞增殖使子宫变得不应答。通过RNA测序进行的高通量基因表达分析表明，胰岛素样生长因子1（IGF1）途径是在E2作用下关闭着床窗口的候选途径。向延迟着床小鼠施用IGF1导致LE细胞增殖。
本研究表明，子宫容受性窗口由E2关闭，这是由IGF1途径介导的。
