The endometrium, a complex and dynamic tissue lining the inner wall of the uterus, undergoes cyclical changes regulated by estrogen and progesterone fluctuations throughout a woman's life. These hormones play crucial roles in maintaining reproductive health, including menstrual cycles, fertility, and pregnancy. The endometrium's biology involves intricate paracrine interactions between epithelial and stromal cells, modulated by estrogen and progesterone levels. Understanding the signaling pathways of estrogen and progesterone receptors (ER and PR) is essential for elucidating normal reproductive physiology and addressing hormonal imbalances that can lead to gynecological conditions and tumorigenesis. The endometrium consists of two main layers: the basal layer and the functional layer. The basal layer remains relatively stable, hosting endometrial progenitor/stem cells, while the functional layer undergoes cyclical morphological and functional changes in response to ovarian hormones. These changes are critical for embryo implantation and pregnancy development. The endometrium exhibits high regenerative capacity, with approximately 450 cycles of shedding and regeneration throughout a woman's lifetime. Estrogen and progesterone signaling in the endometrium are complex and involve both genomic and non-genomic pathways. Estrogen signaling, primarily mediated by ERα, regulates epithelial cell proliferation and differentiation, while progesterone signaling, mediated by PR-A and PR-B, promotes decidualization and receptivity. Key mediators such as IGF-1, C/EBPβ, LIF, EGR1, and COUP-TFII play crucial roles in these processes. The balance between ERα and PR signaling is essential for maintaining the homeostasis of epithelial cell proliferation and preventing uterine anomalies. Recent advances in research models, including murine models and 3D human endometrial organoids, have enhanced our understanding of ER and PR signaling in the endometrium. These models provide insights into the molecular mechanisms regulating endometrial functions and contribute to the development of more effective therapeutic strategies in women's health.The endometrium, a complex and dynamic tissue lining the inner wall of the uterus, undergoes cyclical changes regulated by estrogen and progesterone fluctuations throughout a woman's life. These hormones play crucial roles in maintaining reproductive health, including menstrual cycles, fertility, and pregnancy. The endometrium's biology involves intricate paracrine interactions between epithelial and stromal cells, modulated by estrogen and progesterone levels. Understanding the signaling pathways of estrogen and progesterone receptors (ER and PR) is essential for elucidating normal reproductive physiology and addressing hormonal imbalances that can lead to gynecological conditions and tumorigenesis. The endometrium consists of two main layers: the basal layer and the functional layer. The basal layer remains relatively stable, hosting endometrial progenitor/stem cells, while the functional layer undergoes cyclical morphological and functional changes in response to ovarian hormones. These changes are critical for embryo implantation and pregnancy development. The endometrium exhibits high regenerative capacity, with approximately 450 cycles of shedding and regeneration throughout a woman's lifetime. Estrogen and progesterone signaling in the endometrium are complex and involve both genomic and non-genomic pathways. Estrogen signaling, primarily mediated by ERα, regulates epithelial cell proliferation and differentiation, while progesterone signaling, mediated by PR-A and PR-B, promotes decidualization and receptivity. Key mediators such as IGF-1, C/EBPβ, LIF, EGR1, and COUP-TFII play crucial roles in these processes. The balance between ERα and PR signaling is essential for maintaining the homeostasis of epithelial cell proliferation and preventing uterine anomalies. Recent advances in research models, including murine models and 3D human endometrial organoids, have enhanced our understanding of ER and PR signaling in the endometrium. These models provide insights into the molecular mechanisms regulating endometrial functions and contribute to the development of more effective therapeutic strategies in women's health.