Author/Authors :
Kobayashi, Ryosuke Laboratory of Animal Morphology - Division of Biofunctional Development - Graduate School of Bioagricultural Sciences - Nagoya University, Nagoya, Japan , Terakawa, Jumpei Laboratory of Animal Morphology - Division of Biofunctional Development - Graduate School of Bioagricultural Sciences - Nagoya University, Nagoya, Japan , Omatsu, Tsutomu Research and Education Center for Prevention of Global Infectious Diseases of Animals - Tokyo University of Agriculture and Technology, Tokyo, Japan , Hengjan, Yupadee Laboratory of Animal Morphology - Division of Biofunctional Development - Graduate School of Bioagricultural Sciences - Nagoya University, Nagoya, Japan , Mizutani, Tetsuya Research and Education Center for Prevention of Global Infectious Diseases of Animals - Tokyo University of Agriculture and Technology, Tokyo, Japan , Ohmori, Yasushige Laboratory of Animal Morphology - Division of Biofunctional Development - Graduate School of Bioagricultural Sciences - Nagoya University, Nagoya, Japan , Hondo, Eiichi Laboratory of Animal Morphology - Division of Biofunctional Development - Graduate School of Bioagricultural Sciences - Nagoya University, Nagoya, Japan
Abstract :
Background: 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.
Methods: 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.
Results: 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. In vivo administration of IGF1 to delayed implantation
mice resulted in proliferation in the LE cells.
Conclusion: This study demonstrated that the window of uterine receptivity was closed by E2, which was mediated by the IGF1 pathway.
Keywords :
Embryo implantation , Estrogen , Insulin-like growth factor 1 , Mouse
