In human, the hormonal regulation is crucial for preparing uterine environment leading to either successful implantation or menstrual cycle. Estrogen is a pivotal female steroid hormone to regulate uterine dynamics with progesterone in the estrous cycle and the menstrual cycle in human. Estrogen signals through either the nuclear estrogen receptor or membrane-bound receptor. The membrane-bound estrogen receptor plays a crucial role in rapid response of estrogen in the uterine epithelium. Recently, RASD1 has been attending as a novel signaling transducer of estrogen in various systems including female reproductive organs. In this review, we explain regulation of estrogen and RASD1 signaling in the uterus and also we insight implication of RAS as a novel signaling in repeated implantation failure.